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π CHEMO 4 β EXAM NOTES
1. ANTIFUNGAL AGENTS
Fungal infections are common in diabetics, cancer patients, AIDS, pregnancy, and people on broad-spectrum antibiotics or immunosuppressants.
Classification of Antifungal Drugs
| Category | Examples |
|---|---|
| Polyenes (Antibiotics) | Amphotericin B, Nystatin, Hamycin |
| Antimetabolite | Flucytosine |
| Azoles β Imidazoles (Topical) | Clotrimazole, Econazole, Miconazole, Oxiconazole |
| Azoles β Imidazoles (Systemic) | Ketoconazole |
| Azoles β Triazoles | Fluconazole, Itraconazole, Voriconazole, Posaconazole |
| Heterocyclic benzofuran | Griseofulvin |
| Echinocandins | Caspofungin, Micafungin, Anidulafungin |
| Allylamines | Terbinafine |
| Topical agents | Tolnaftate, Undecylenic acid, Butenafine, etc. |
AMPHOTERICIN B (AMB)
What it is: Broad-spectrum antifungal antibiotic
Works against: Cryptococcus, Coccidioides, Candida, Aspergillus, Blastomyces, Histoplasma, Sporothrix, Mucormycosis
Pharmacokinetics (How it moves in body)
- β NOT absorbed from gut β cannot be given orally for systemic infections
- Highly bound to plasma proteins and tissues
- Does NOT cross the blood-brain barrier (BBB)
- Metabolized in liver, excreted slowly in urine and bile
Mechanism of Action
Fungi have ergosterol in their cell membrane (like cholesterol in human cells)
AMB β binds to ergosterol β forms pores/channels β membrane leaks β fungus dies (fungicidal)
(Same mechanism for Nystatin and Hamycin)
Adverse Effects
- Fever, chills, headache, shortness of breath
- GI disturbances
- Phlebitis (vein inflammation) at injection site
Uses
- Systemic mycoses β mucormycosis, aspergillosis, cryptococcosis, sporotrichosis, histoplasmosis, blastomycosis
- Topical β oral and cutaneous candidiasis
- L-AMB (Liposomal AMB) β used in leishmaniasis and febrile neutropenia
AZOLES
Types: Imidazoles + Triazoles (same mechanism, similar spectrum)
Mechanism of Action
- Azoles block 14Ξ±-demethylase β stop conversion of lanosterol β ergosterol
- Terbinafine blocks squalene 2,3-epoxidase β stop squalene β lanosterol
- Result: No ergosterol made β fungal cell membrane damaged
2. ANTI-AMOEBIC DRUGS
Amoebiasis = protozoal infection by E. histolytica, spread by faeco-oral route
Classification
Antiamoebic Drugs
βββ Tissue Amoebicides
β βββ For intestinal + extraintestinal: Nitroimidazoles (Metronidazole, Tinidazole...)
β β Alkaloids (Emetine, Dehydroemetine)
β βββ For extraintestinal only: Chloroquine
βββ Luminal Amoebicides
βββ Amides: Diloxanide furoate, Nitazoxanide
βββ Antibiotics: Tetracycline, Paromomycin
βββ 8-Hydroxyquinolines: Iodoquinol, Diiodohydroxyquin
METRONIDAZOLE β (Most Important)
What it is: Nitroimidazole derivative
Works against: E. histolytica, Giardia lamblia, Trichomonas vaginalis, anaerobic bacteria
Mechanism of Action
It is a prodrug β gets activated inside the microorganism
Metronidazole enters β 'Nitro' group accepts electrons from ferredoxins β forms reactive nitro radical β damages microbial DNA β organism dies (cidal)
Pharmacokinetics
- Given: oral, IV, topical
- Well absorbed in small intestine
- Poorly bound to plasma proteins
- Crosses into brain β
- Metabolized in liver, excreted in urine
Uses & Doses
| Condition | Dose |
|---|---|
| Amoebiasis (intestinal + extraintestinal) | 400β800 mg TDS Γ 7β10 days |
| Trichomonas vaginitis | 400 mg TDS Γ 7 days (treat both partners!) |
| Giardiasis | 200 mg TDS Γ 7 days |
| Anaerobic infections | Highly effective (PID, lung abscess, B. fragilis, Clostridium) |
| Others | Bacterial vaginosis, guinea worm, Crohn's disease |
Treatment of Amoebiasis (Table Summary)
| Situation | Treatment |
|---|---|
| Asymptomatic carrier | Diloxanide furoate or Paromomycin or Iodoquinol |
| Intestinal amoebiasis | Metronidazole 400 mg TDS + Diloxanide furoate 500 mg TDS Γ 7β10 days |
| Severe amoebic dysentery | Same as above OR Metronidazole IV 500 mg q6h till oral tolerated |
| Hepatic amoebiasis | Metronidazole + luminal agent; add Chloroquine if no response |
Adverse Effects
- GIT: Nausea, metallic taste, dry mouth, cramps, vomiting
- Allergy: Skin rash, urticaria, flushing
- CNS: Dizziness, confusion, headache; polyneuropathy on long-term use
- β οΈ Alcohol: Causes nausea, vomiting, flushing β avoid alcohol during treatment!
3. ANTHELMINTICS (Worm-killing drugs)
Helminths = worms (Roundworms/Nematodes + Flatworms: Flukes + Tapeworms)
Key Drugs: Mebendazole, Albendazole, Niclosamide, Ivermectin, Pyrantel pamoate, Levamisole
MEBENDAZOLE vs ALBENDAZOLE
| Feature | Mebendazole | Albendazole |
|---|---|---|
| Mechanism | Binds Ξ²-tubulin β blocks microtubule formation + blocks glucose transport β worm immobilized/dies slowly | Same as Mebendazole |
| Absorption | Poorly absorbed orally | Erratically absorbed; fatty food increases absorption |
| Metabolism | Liver | Liver β active metabolite: albendazole sulphoxide |
| Distribution | Poor | Widely distributed incl. hydatid cyst |
| Main uses | Roundworm, hookworm, whipworm, pinworm, mixed worm; better in trichuriasis | Same nematodes; better in neurocysticercosis, hydatid disease, filariasis |
| Dose | 100 mg BD Γ 3 days | Single dose 400 mg (adults & children >2 yrs); 200 mg if 1β2 yrs |
| Adverse effects | Rare GI (anorexia, nausea, diarrhoea); CI in pregnancy + children <1 yr | Rare GI; long-term: hepatic dysfunction, hair loss, neutropenia |
| Fasting/purging needed? | No | No |
Albendazole Special Uses
- Neurocysticercosis β with praziquantel
- Hydatid disease β drug of choice for medical treatment (surgery = first choice)
- Filariasis β 400 mg + DEC (diethylcarbamazine) or ivermectin
4. ANTICANCER DRUGS
Toxicity of Cytotoxic Drugs
Anticancer drugs kill fast-dividing cells β cancer cells AND normal fast-dividing cells
Most affected normal cells: Bone marrow, skin, hair, GI mucosa, reticuloendothelial system, gonads, fetus
General Toxicity
| Side Effect | Details | Management |
|---|---|---|
| Bone marrow suppression | Leucopenia, thrombocytopenia, aplastic anaemia β infections + bleeding | Platelet transfusion, G-CSF, Erythropoietin, Bone marrow transplant; use marrow-sparing drugs (L-asparaginase, bleomycin, cisplatin, vincristine) |
| Immunosuppression | β Lymphocytes β opportunistic infections (Candida, CMV, P. jiroveci) | β |
| GIT | Nausea & vomiting (CTZ stimulation) | 5-HT3 antagonists: ondansetron, granisetron; also metoclopramide, dexamethasone |
| Skin & Hair | Alopecia (reversible on stopping), dermatitis, skin rashes | β |
| Gonads | Oligozoospermia, infertility (males); amenorrhoea (females) | β |
| Fetus | Abortion or teratogenicity | Avoid in pregnancy |
| Hyperuricaemia | Excess cell breakdown β uric acid β gout/stones | Hydration, allopurinol, corticosteroids |
| Hypercalcaemia | Due to malignancy or drugs | Hydration, bisphosphonates, corticosteroids |
| Secondary malignancy | Rare; e.g. leukaemia with alkylating agents | β |
Specific Toxicity
| Drug | Specific Toxicity | Treatment |
|---|---|---|
| Cyclophosphamide | Haemorrhagic cystitis | Mesna (systemic) + acetylcysteine (local) |
| Methotrexate | Megaloblastic anaemia | Folinic acid / leucovorin / citrovorum factor |
| Cisplatin | Nephrotoxicity | Saline infusion + mannitol |
| Vincristine / Paclitaxel | Neuropathy | β |
| Busulphan / Bleomycin | Pulmonary fibrosis + skin pigmentation | β |
| Doxorubicin / Daunorubicin | Cardiotoxicity | Dexrazoxane (iron chelating agent) |
HORMONES & HORMONE ANTAGONISTS (in Cancer)
| Drug | Type | Use |
|---|---|---|
| Glucocorticoids | Anti-inflammatory, lympholytic | Leukaemias, lymphomas; also reduce oedema, hypersensitivity, hypercalcaemia; boost antiemetics |
| Oestrogens | Androgen antagonist | Prostate cancer; Fosfestrol (prodrug β active in prostate) |
| Tamoxifen | Anti-oestrogen | Palliative treatment of hormone-dependent breast cancer |
| Progestins | β | Endometrial carcinoma |
| Flutamide | Non-steroidal anti-androgen | Blocks androgen receptor β prostate cancer |
| Finasteride | 5Ξ±-reductase inhibitor | Blocks testosterone β DHT; prostate cancer + BPH |
| Aromatase inhibitors | Block oestrogen synthesis | Hormone-dependent breast cancer (postmenopausal women) |
| GnRH agonists (buserelin, goserelin, leuprolide) | Pulsatile: βFSH/LH; Continuous: β pituitary gonadotropins | Palliative in prostate + breast cancer |
Classification of Anticancer (Cytotoxic) Drugs
Alkylating Agents:
- Nitrogen mustards: Mechlorethamine, Cyclophosphamide, Ifosfamide, Chlorambucil, Melphalan
- Ethylenimine: Thiotepa
- Alkylsulfonate: Busulphan
- Nitrosoureas: Carmustine, Lomustine
- Triazines: Dacarbazine, Temozolomide
- Platinum complexes: Cisplatin, Carboplatin, Oxaliplatin
- Methyl hydrazine: Procarbazine
Antimetabolites:
- Folate antagonists: Methotrexate, Pemetrexed
- Purine antagonists: 6-Mercaptopurine, 6-Thioguanine, Azathioprine, Fludarabine
- Pyrimidine antagonists: 5-Fluorouracil, Capecitabine, Cytarabine
β‘ QUICK RECALL TIPS
| Memory Hook | Fact |
|---|---|
| AMB = Awful Many Bad effects | Fever, chills, nephrotoxicity β but gold standard for serious fungal infection |
| Metro = METAL taste | Metallic taste is classic side effect of metronidazole |
| Metro + Alcohol = Disaster | Disulfiram-like reaction |
| Mebendazole Ξ²-tubulin | Mebe-ndazole = no microtubules |
| Albendazole = All body | Reaches hydatid cyst, brain (neurocysticercosis) |
| Ondan-setron for vomiting | 5-HT3 blocker for chemo-induced nausea |
| Tamoxifen = Breast | Anti-oestrogen β breast cancer |
| Flutamide = Prostate | Anti-androgen β prostate cancer |
| Cisplatin β kidney damage | Prevent with saline + mannitol |
| Doxorubicin β heart damage | Prevent with dexrazoxane |
Complete anticancer drugs
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Now I have enough from the textbook. Let me compile comprehensive, exam-ready notes on all anticancer drugs.
π― COMPLETE ANTICANCER DRUGS β EXAM NOTES
OVERVIEW
Cancer chemotherapy aims to cause apoptosis or lethal damage in cancer cells. Attack is directed at:
- DNA (alkylating agents, platinum drugs, antibiotics)
- DNA precursors (antimetabolites)
- Cell division machinery (microtubule inhibitors)
- Hormonal signalling (hormone antagonists)
- Immune/targeted pathways (biologicals)
CLASSIFICATION OF ANTICANCER DRUGS
ANTICANCER DRUGS
βββ 1. Cytotoxic Drugs
β βββ Alkylating Agents
β β βββ Nitrogen mustards: Cyclophosphamide, Mechlorethamine, Ifosfamide, Chlorambucil, Melphalan
β β βββ Ethylenimine: Thiotepa
β β βββ Alkylsulfonate: Busulphan
β β βββ Nitrosoureas: Carmustine, Lomustine
β β βββ Triazines: Dacarbazine, Temozolomide
β β βββ Platinum complexes: Cisplatin, Carboplatin, Oxaliplatin
β βββ Antimetabolites
β β βββ Folate antagonists: Methotrexate, Pemetrexed
β β βββ Purine antagonists: 6-MP, 6-TG, Azathioprine, Fludarabine
β β βββ Pyrimidine antagonists: 5-FU, Capecitabine, Cytarabine, Gemcitabine
β βββ Antitumour Antibiotics: Doxorubicin, Bleomycin, Dactinomycin, Mitomycin C
β βββ Microtubule (Spindle) Inhibitors
β βββ Vinca alkaloids: Vincristine, Vinblastine
β βββ Taxanes: Paclitaxel, Docetaxel
βββ 2. Hormones & Antagonists
β βββ Glucocorticoids, Oestrogens, Progestins
β βββ Tamoxifen, Aromatase inhibitors
β βββ Antiandrogens (Flutamide, Finasteride)
β βββ GnRH agonists (Leuprolide, Goserelin)
βββ 3. Targeted Therapy
β βββ Kinase inhibitors: Imatinib, Erlotinib, etc.
β βββ Monoclonal antibodies: Rituximab, Trastuzumab, etc.
βββ 4. Miscellaneous: Thalidomide, Bortezomib, Abiraterone, L-asparaginase
PART 1: ALKYLATING AGENTS
Basic Mechanism:
All alkylating agents add an alkyl group to DNA (mainly to guanine at N-7 position) β cross-linking of DNA strands β DNA cannot replicate β cell dies
They are cell cycle non-specific (kill cells in any phase).
A. NITROGEN MUSTARDS
CYCLOPHOSPHAMIDE β (Most Important)
| Feature | Detail |
|---|---|
| Type | Prodrug β activated in liver to acrolein + phosphoramide mustard |
| MOA | Cross-links DNA strands β cell death |
| Route | Oral or IV |
| Uses | Lymphomas, breast cancer, ovarian cancer, leukaemias, autoimmune diseases (as immunosuppressant) |
| Key Side Effect | Haemorrhagic cystitis (due to acrolein irritating bladder) |
| Prevention | Give mesna (systemically) + acetylcysteine (locally) + good hydration |
| Other ADRs | Alopecia, bone marrow suppression, nausea/vomiting |
OTHER NITROGEN MUSTARDS
| Drug | Main Use |
|---|---|
| Mechlorethamine | Hodgkin's lymphoma (MOPP regimen) |
| Chlorambucil | CLL (chronic lymphocytic leukaemia) |
| Melphalan | Multiple myeloma |
| Ifosfamide | Sarcomas, testicular cancer (also causes haemorrhagic cystitis β give mesna) |
B. BUSULPHAN
| Feature | Detail |
|---|---|
| MOA | Alkylsulfonate β alkylates DNA |
| Use | Chronic myeloid leukaemia (CML), bone marrow conditioning before transplant |
| Key Toxicity | Pulmonary fibrosis (busulphan lung) + skin pigmentation ("Addisonian pigmentation") |
C. NITROSOUREAS (Carmustine, Lomustine)
| Feature | Detail |
|---|---|
| Special property | Cross the blood-brain barrier (BBB) β |
| Uses | Brain tumours (gliomas), Hodgkin's lymphoma |
| ADRs | Myelosuppression (delayed, 4β6 weeks), nausea |
D. DACARBAZINE & TEMOZOLOMIDE (Triazines)
| Feature | Dacarbazine | Temozolomide |
|---|---|---|
| Activation | Requires liver CYP450 | Spontaneous at physiological pH |
| BBB crossing | β No | β Yes |
| Uses | Melanoma, Hodgkin's lymphoma | Brain tumours (glioblastoma, astrocytoma), melanoma |
| Route | IV | Oral or IV |
E. PLATINUM COMPLEXES β
CISPLATIN
| Feature | Detail |
|---|---|
| MOA | Forms intra- and inter-strand crosslinks with DNA (at N-7 of guanine) β inhibits DNA replication |
| Uses | Testicular cancer β, ovarian, bladder, lung, head & neck cancers |
| Key Toxicity | Nephrotoxicity (most important) + neurotoxicity + ototoxicity (tinnitus, hearing loss) |
| Prevention of nephrotoxicity | Aggressive IV saline hydration + mannitol (forced diuresis) |
| Other ADRs | Severe nausea/vomiting (most emetogenic chemo drug), hypomagnesaemia, hypokalaemia |
CARBOPLATIN
- Less nephrotoxic and neurotoxic than cisplatin
- Main toxicity: myelosuppression
- Used when patient can't tolerate cisplatin
- Dose calculated using AUC formula (Calvert formula)
OXALIPLATIN
- Used in colorectal cancer
- Special toxicity: Cold-triggered peripheral neuropathy (don't touch cold objects!)
- Also causes cumulative neurotoxicity
PART 2: ANTIMETABOLITES
Basic Mechanism:
These drugs resemble normal building blocks (folate, purines, pyrimidines) but block their use β DNA/RNA synthesis stops β cell death
They are cell cycle specific (S phase).
A. FOLATE ANTAGONISTS
METHOTREXATE (MTX) β
| Feature | Detail |
|---|---|
| MOA | Inhibits dihydrofolate reductase (DHFR) β blocks conversion of dihydrofolate to tetrahydrofolate (THF) β no thymidylate synthesis β no DNA |
| Uses | ALL (acute lymphoblastic leukaemia), choriocarcinoma, breast cancer, osteosarcoma, lymphomas, psoriasis, rheumatoid arthritis |
| Key Toxicity | Megaloblastic anaemia, mucositis, bone marrow suppression, hepatotoxicity |
| Antidote/Rescue | Folinic acid (leucovorin/citrovorum factor) β given 24h after MTX to "rescue" normal cells |
| Other | Can be given intrathecally for meningeal leukaemia; doesn't cross BBB well otherwise |
PEMETREXED
- Multi-enzyme inhibitor (DHFR + thymidylate synthase)
- Used in non-small cell lung cancer (NSCLC) and mesothelioma
- Give folic acid + B12 supplements to reduce toxicity
B. PURINE ANTAGONISTS
| Drug | Special Feature | Main Use |
|---|---|---|
| 6-Mercaptopurine (6-MP) | Prodrug; metabolized by HGPRT β blocks purine synthesis | ALL maintenance therapy |
| 6-Thioguanine | Similar to 6-MP | Leukaemias |
| Azathioprine | Prodrug converted to 6-MP; mainly immunosuppressant | Organ transplant rejection, autoimmune diseases |
| Fludarabine | Resistant to adenosine deaminase | CLL, low-grade lymphomas |
β οΈ 6-MP toxicity increased by allopurinol β allopurinol blocks xanthine oxidase which metabolizes 6-MP β dose reduction needed
C. PYRIMIDINE ANTAGONISTS
5-FLUOROURACIL (5-FU) β
| Feature | Detail |
|---|---|
| MOA | Converted to FdUMP β inhibits thymidylate synthase β blocks thymidylate (TMP) synthesis β no DNA |
| Uses | Colorectal cancer β, breast cancer, stomach, pancreatic cancer; topical for skin cancers |
| ADRs | Mucositis, diarrhoea, myelosuppression, hand-foot syndrome (palmar-plantar erythrodysaesthesia) |
| Rescue | Leucovorin enhances 5-FU effect (used together) |
CAPECITABINE
- Oral prodrug of 5-FU
- Activated in tumour tissue β 5-FU
- Used in breast and colorectal cancer
CYTARABINE (Ara-C)
- Pyrimidine analog β inhibits DNA polymerase
- Not given orally (deaminated in gut)
- Main use: Acute myeloid leukaemia (AML)
- Intrathecal for meningeal leukaemia
GEMCITABINE
- Analog of deoxycytidine
- Main use: Pancreatic cancer, non-small cell lung cancer
- Given IV
PART 3: ANTITUMOUR ANTIBIOTICS
Produced from Streptomyces bacteria. Act mainly by intercalating DNA or generating free radicals.
ANTHRACYCLINES β
| Drug | Feature |
|---|---|
| Doxorubicin (Adriamycin) | Most widely used; intercalates DNA + inhibits topoisomerase II |
| Daunorubicin | Used in leukaemias |
| Epirubicin, Idarubicin | Similar to doxorubicin |
Key Toxicity: CARDIOTOXICITY (dilated cardiomyopathy) β cumulative dose-dependent
- Prevention: Dexrazoxane (iron chelating agent that prevents free radical cardiac damage)
- Also: alopecia, myelosuppression, nausea, "red urine"
BLEOMYCIN
| Feature | Detail |
|---|---|
| MOA | Causes DNA strand breaks via free radicals |
| Uses | Testicular cancer, Hodgkin's lymphoma, squamous cell carcinomas |
| Key Toxicity | Pulmonary fibrosis + skin pigmentation (does NOT cause significant myelosuppression) |
DACTINOMYCIN (Actinomycin D)
- Intercalates DNA
- Used in: Wilm's tumour, choriocarcinoma, rhabdomyosarcoma
MITOMYCIN C
- Cross-links DNA
- Used in bladder, gastric, cervical cancer
PART 4: MICROTUBULE (SPINDLE) INHIBITORS
Basic Mechanism: Affect tubulin β interfere with mitotic spindle β cell arrested in M phase
VINCA ALKALOIDS (from Vinca rosea plant)
| Drug | MOA | Uses | Key Toxicity |
|---|---|---|---|
| Vincristine | Inhibits tubulin polymerization β no spindle formation | ALL, Hodgkin's lymphoma, Wilm's | Peripheral neuropathy β (paresthesia, foot-drop); minimal myelosuppression |
| Vinblastine | Same | Testicular cancer, Hodgkin's | Myelosuppression (more than vincristine) |
Memory: Vincris-TINE = Tin-gling (neuropathy) | Vinblas-TINE = Blood (myelosuppression)
TAXANES
| Drug | MOA | Uses | Key Toxicity |
|---|---|---|---|
| Paclitaxel | Stabilizes microtubules β prevents spindle disassembly β cell stuck in mitosis | Ovarian, breast, lung cancers | Neuropathy, myelosuppression, hypersensitivity (premedicate!) |
| Docetaxel | Same | Breast, prostate, NSCLC | Fluid retention, neuropathy, myelosuppression |
β οΈ Vinca alkaloids = inhibit polymerization | Taxanes = stabilize microtubules (opposite mechanism, same result)
PART 5: HORMONES & HORMONE ANTAGONISTS
1. GLUCOCORTICOIDS (e.g. Prednisolone, Dexamethasone)
Why used in cancer?
- Marked lympholytic effect β kill lymphocytes
- Reduce oedema around tumour
- Anti-nausea (enhance antiemetics)
- Reduce hypersensitivity reactions
- Control hypercalcaemia
- Produce feeling of well-being
Uses: ALL, lymphomas, brain tumour oedema, supportive care
2. OESTROGENS
- Fosfestrol β activated to stilboestrol in prostate tissue
- Used in prostate cancer (antagonizes androgens)
3. TAMOXIFEN β
| Feature | Detail |
|---|---|
| Type | Selective Oestrogen Receptor Modulator (SERM) β anti-oestrogen in breast |
| MOA | Blocks oestrogen receptors in breast tissue |
| Use | Hormone receptor-positive breast cancer (palliative + adjuvant) |
| ADRs | Hot flashes, thromboembolism, endometrial cancer (long-term use) |
4. AROMATASE INHIBITORS
- Anastrozole, Letrozole, Exemestane
- Block conversion of androgens β oestrogen in peripheral tissues
- Used in postmenopausal women with hormone-dependent breast cancer
- First-line for ER+ breast cancer in postmenopausal women
- ADRs: Hot flashes, bone loss (osteoporosis), arthralgia
5. PROGESTINS
- Medroxyprogesterone, Megestrol
- Used in endometrial carcinoma
6. ANTIANDROGENS
| Drug | Type | Use |
|---|---|---|
| Flutamide | Non-steroidal β blocks androgen receptor | Prostate cancer |
| Bicalutamide | Non-steroidal β blocks androgen receptor | Prostate cancer (better tolerated) |
| Finasteride | 5Ξ±-reductase inhibitor β blocks testosterone β DHT | Prostate cancer + BPH |
7. GnRH AGONISTS β
| Drug | Detail |
|---|---|
| Leuprolide, Goserelin, Triptorelin, Buserelin | |
| MOA | Continuous use β desensitizes GnRH receptors in pituitary β β LH + FSH β β testosterone (males) + β oestrogen (females) |
| Initial effect | Transient tumour flare (first 2 weeks) due to initial LH/FSH rise β combine with antiandrogen initially |
| Uses | Prostate cancer, breast cancer, endometriosis, uterine fibroids |
| ADRs | Hot flashes, sexual dysfunction, decreased bone density |
PART 6: TARGETED THERAPY
A. KINASE INHIBITORS (Small Molecule)
| Drug | Target | Use |
|---|---|---|
| Imatinib (Gleevec) | BCR-ABL tyrosine kinase | CML β (Philadelphia chromosome positive) |
| Erlotinib, Gefitinib | EGFR tyrosine kinase | NSCLC (EGFR mutated) |
| Sorafenib | Multikinase (VEGFR, RAF) | Hepatocellular carcinoma, renal cell carcinoma |
| Vemurafenib | BRAF V600E mutant | Melanoma |
B. MONOCLONAL ANTIBODIES
| Drug | Target | Use |
|---|---|---|
| Rituximab | Anti-CD20 | B-cell lymphomas, CLL |
| Trastuzumab (Herceptin) | Anti-HER2/neu | HER2+ breast cancer |
| Bevacizumab (Avastin) | Anti-VEGF (angiogenesis) | Colorectal, lung, renal cancers |
| Cetuximab | Anti-EGFR | Colorectal, head & neck cancers |
C. IMMUNOTHERAPY (Checkpoint Inhibitors)
| Drug | Target | Use |
|---|---|---|
| Pembrolizumab, Nivolumab | Anti-PD-1 | Melanoma, NSCLC, many others |
| Atezolizumab, Avelumab | Anti-PD-L1 | NSCLC, bladder cancer |
| Ipilimumab | Anti-CTLA-4 | Melanoma |
MOA: These drugs remove the "brakes" on T cells β immune system attacks cancer cells
PART 7: MISCELLANEOUS DRUGS
L-ASPARAGINASE
- Enzyme that breaks down asparagine
- Tumour cells (ALL cells) cannot make asparagine β depend on blood supply β L-asparaginase depletes it β tumour cells starve
- Bone marrow-sparing drug β
- Used in: ALL (especially in children)
- ADRs: Pancreatitis, coagulopathy, hypersensitivity
THALIDOMIDE, LENALIDOMIDE, POMALIDOMIDE
- Multiple myeloma treatment
- Antiangiogenic + immunomodulatory
- β οΈ Teratogenic (thalidomide caused phocomelia β limb defects)
- ADRs: Thromboembolism, myelosuppression
BORTEZOMIB (Proteasome inhibitor)
- Prevents protein degradation β pro-apoptotic factors accumulate β cancer cell dies
- Used in multiple myeloma and mantle cell lymphoma
- ADRs: Neuropathy (give SC not IV), myelosuppression, herpes zoster (give antiviral prophylaxis)
ABIRATERONE
- Inhibits CYP17 (androgen synthesis enzyme)
- Used in castration-resistant prostate cancer
- Always given with prednisone (to prevent mineralocorticoid excess)
TOXICITY β COMPLETE SUMMARY TABLE
General Toxicity (All Cytotoxic Drugs)
| Toxicity | Details | Management |
|---|---|---|
| Bone marrow suppression | Leucopenia, thrombocytopenia, anaemia | G-CSF (filgrastim), erythropoietin, platelet transfusion, bone marrow transplant |
| GI effects | Nausea, vomiting, mucositis, diarrhoea | Ondansetron, granisetron (5-HT3 blockers); dexamethasone, metoclopramide |
| Alopecia | Hair follicle damage | Reversible on stopping therapy |
| Immunosuppression | Risk of opportunistic infections (Candida, CMV, PCP) | Prophylactic antifungals/antivirals |
| Gonadal toxicity | Oligospermia, amenorrhoea, infertility | Sperm banking before chemotherapy |
| Foetal harm | Teratogenicity, abortion | Contraindicated in pregnancy |
| Hyperuricaemia | Cell lysis β uric acid release β gout/kidney stones | Allopurinol, hydration, rasburicase |
| Hypercalcaemia | From malignancy or drugs | Hydration, bisphosphonates, steroids |
| Secondary malignancy | Alkylating agents β leukaemia (rare) | β |
Drug-Specific Toxicity (MUST MEMORIZE)
| Drug | Specific Toxicity | Prevention/Antidote |
|---|---|---|
| Cyclophosphamide/Ifosfamide | Haemorrhagic cystitis | Mesna + acetylcysteine + hydration |
| Methotrexate | Megaloblastic anaemia, mucositis | Folinic acid (leucovorin) rescue |
| Cisplatin | Nephrotoxicity, ototoxicity, neurotoxicity | Saline hydration + mannitol |
| Doxorubicin/Daunorubicin | Cardiotoxicity (dilated cardiomyopathy) | Dexrazoxane; limit cumulative dose |
| Bleomycin/Busulphan | Pulmonary fibrosis + skin pigmentation | Avoid O2 toxicity; monitor DLCO |
| Vincristine/Paclitaxel | Peripheral neuropathy | Dose reduction |
| Tamoxifen | Endometrial cancer, thromboembolism | Annual endometrial monitoring |
CELL CYCLE SPECIFICITY
| Phase Specific | Non-Phase Specific (Cell Cycle NS) |
|---|---|
| S phase: Antimetabolites (MTX, 5-FU, cytarabine) | Alkylating agents |
| M phase: Vinca alkaloids, taxanes | Antitumour antibiotics (most) |
| β | Platinum compounds |
β‘ QUICK RECALL TABLE β HIGH-YIELD EXAM FACTS
| Drug | Remember |
|---|---|
| Cisplatin | Most emetogenic + nephrotoxic β saline + mannitol |
| Cyclophosphamide | Haemorrhagic cystitis β mesna |
| Doxorubicin | Red urine + heart damage β dexrazoxane |
| Bleomycin | Lung fibrosis β no myelosuppression |
| Busulphan | CML + lung fibrosis + pigmentation |
| Methotrexate | DHFR inhibitor β rescue with folinic acid |
| Vincristine | Neuropathy (NOT myelosuppression) |
| Vinblastine | Myelosuppression (NOT neuropathy) |
| Taxanes | Stabilize microtubules (Vinca = destabilize) |
| Imatinib | CML, BCR-ABL = Philadelphia chromosome |
| Tamoxifen | Breast cancer (ER+) β risk endometrial cancer |
| Aromatase inhibitors | Postmenopausal breast cancer |
| GnRH agonists | Continuous = suppress (tumour flare at start) |
| Nitrosoureas | Cross BBB β brain tumours |
| Temozolomide | Brain tumours β crosses BBB, oral |
| L-Asparaginase | ALL β bone marrow-sparing |
| Bortezomib | Multiple myeloma β give SC to reduce neuropathy |
| Rituximab | CD20 β B cell lymphoma |
| Trastuzumab | HER2+ β breast cancer |
Sources: Lippincott Illustrated Reviews Pharmacology, Johari Pharmacology
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