Antineoplastic Drugs

Antineoplastic Drugs Anntttiiim 1.. An m meettaaab bbo olli lit iittteeess 1 2. D C 2. DN N NA A & Cel Ceeellllllu uulllaaarr ddiivvi vis iisssiiio oon n 3. K innh nnaaall aan odiieeess 3. Kiiin nnas naaasssee in hhiiib biittto oor ors mo mon on nno oocccllonal nntttiiib bod rrsss,, m 1..1 “IIm on fol foolllaatteee”””:: meettth euuccco hyyd 1. 1 – “I m miiittaatttii on h ottrrreeex xxaatteee,, leu oov vvo oorr iin nn,, 5--F Fllu uuo oorrro oou uurrraaacc iilll,, hy ddrrro oox xyyu yur uurrreeeaa CA can be treated with targeted radiotherapy, excision (local therapy) or systemic administration of cytotoxic drugs to eradicate or control proliferative cells, but affect systemic as well. CA cells produces larger amounts of DNA/RNA per unit time than most healthy cells, so affecting these pathways is highly attractive. • These agents affect thymidine synthesis, particularly those affecting folate cycle. • Thymidine is a pyrimidine deoxynucleotide (hexagonal plates), synthesized by thymidylate synthetase – methylates dUMP → dTMP (dUMP dumplings → single dumpling with T-shaped chopsticks). Process powered by folate cycle: o Methylated THF (4 leaves + C-shaped sushi) converted to DHF (removing C-shaped sushi & knocking off 2 leaves). Catalyzed thymidylate synthetase. o DHF converted back to THF by DHFR (adding back 2 leaves). THF is then methylated (adding back C-shaped sushi). • Thymidine is only found in DNA. Ribonucleotides are synthesized first. So precursor to both thymidine & uracil is UDP (U Dining in? Please sign in!). Ribonucleotide reductase converts UDP → deoxy-UDP, which is precursor molecule (wait list waitress crossing out oxy). An Ant ntimetabo bol olites • Methotrexate (MTX) (meat stix) o Folate analog competitively & irreversibly binds to DHFR, preventing THF renewal (meat stick chef has blocked leaf boats) → Buildup of folate & DHF (boat jam). Results in blocking de novo synthesis of DNA, RNA, and key cellular proteins. o Cell-cycle specific for S-phase (Sushi Phase, ramen DNA blocked by chopsticks) o Indications ▪ Treats a range of malignancies including leukemias, lymphomas, breast cancer, head & neck cancer, lung CA (cracked cancer crab) ▪ Treats non-neoplastic conditions with abnormal cellular proliferation • MTX + misoprostol as abortifacient (uterus-shaped backpack). Used for non-surgical treatment of early, unruptured ectopic pregnancy (baby keychain outside of uterus). Gestational trophoblastic neoplasia (choriocarcinoma, trophoblastic tumors, invasive molar pregnancy) – most can be treated with short course of MTX (mole for molar pregnancy) • Chronic inflammatory conditions, d/t immunosuppressive effects (torn antibody lantern) o Disease modifying anti-rheumatic drug (DMARDs). Effects take a few weeks (joint lantern with inflammatory candle). May manage with glucocorticoids, NSAIDs for short term SSx relief o Psoriasis (hyperproliferation of epidermis), as well as arthritis & nail disease (potentially d/t immunosuppressive effects) (silvery scaled kneepads) o Other inflammatory conditions, including IBD, SLE, Vasculitides, dermatomyositis o Adverse effects ▪ Folate deficiency (falling foliage) ▪ Megaloblastic (macrocytic) anemia d/t folate deficiency (blasting lanterns) ▪ Myelosuppression is the dose-limiting effect in high dosing needed for chemo. Causes immunosuppression (empty bone serving tray; immunocompromised cane) ▪ Pulmonary fibrosis (restrictive pattern) (restricted growth of lung-shaped bonsai tree) ▪ Hepatotoxicity, likely d/t direct cell damage (liver stain on apron). Monitor LFTs. ▪ Alopecia (bald chef) ▪ Stomatitis (burning mouth with hot meat) o Leucovorin rescue (folinic acid) can be used to reverse or prevent the worst of the adverse effects (maneki-neko, i.e.. lucky feline). Does not require DHFR for activation; displaced MTX from binding sites, restoring normal folate levels. • 5-fluorouracil (5-FU) (full guy waving 5 fingers) o Pyrimidine analog (hexagonal plates). Inhibits thymidylate synthase (guy blocking transfer of C-shaped sushi). Cell-cycle specific for S-phase (Sushi Phase, ramen DNA blocked by chopsticks) o Metabolized to active form, 5-dUMP. Forms complex with thymidylate synthase & DHF. Results in buildup of dUMP (dumpling buildup) o Indications ▪ CRC, breast, head & neck, liver, pancreas CA (cracked cancer crab) ▪ Topically for basal cell carcinoma o Adverse effects ▪ Diarrhea d/t damage of intestinal epithelium (patron with messy pants) ▪ Cutaneous complications • Photosensitivity (camera flash) • Hyperpigmentation • Number of other rashes ▪ Myelosuppression & pancytopenia → immunosuppression (empty bone serving tray; immunocompromised cane) ▪ No leucovorin rescue here! (falling feline) • Hydroxyurea (hydro-rock area) o Inhibits Ribonucleotide reductase (inhibited wait list waitress). Cell-cycle specific for S-phase (Sushi Phase, ramen DNA blocked by chopsticks) o Indications ▪ AML, CML, head & neck CA ▪ Sickle cell anemia, d/t ↑production of HbF (sickle by Zen garden; raising baby with Hb coin up) o Adverse effects ▪ Myelosuppression & pancytopenia → immunosuppression (empty bone serving tray; immunocompromised cane) ▪ GI upset 1..2 chhb of N opprrriiin myyccoop 1. 2 – ““H H Hu uun nch bbaack of No ootttrre D DN N NA A””:: A Azzaattth h iop nneee,, 6--M -MP M MP, pph hheeen nno oolllaaatttee m mo oofffeettiiill P, myc • nucleosides consist of nitrogenous base, ribose, phosphate groups. Purine synthesis begins with phosphoribosyl pyrophosphate (PRPP) (synthesis continues! Pentagon pedestal being built with 3 P-shaped hammers). Metabolized to inosine monophosphate (IMP) (gargoyle imp), which is metabolized to AMP and GMP by separate pathways (gold gramps & grump statues respectively with purine haloes; “Pure As Gold”) Pu Pur uri rine ne ana nalog ogs • Azathioprine (AZA) & 6-mercaptopurine (6-MP) (Aza-merelda with purine earrings; captured gypsy) o AZA is converted to 6-MP, which must be activated by hypoxanthine-guanine phosphoribosyl transferase (HGPRT) (high priest activated captive). Blocks synthesis of IMP (knocking over gargoyle imp) → halting DNA & RNA synthesis o Cell cycle specific for S-phase (dilapidated stairs) o Indications ▪ Hematologic malignancy (cracked cancer crab, antibody archers, and T-cell knights in rose window) ▪ Chronic inflammatory conditions, d/t immunosuppressive effects (torn antibody lantern). Include treatment of graft rejection, SLE, autoimmune hemolytic anemia, inflammatory myopathies, IBD (inflamed colonic haustra lanterns) ▪ Disease modifying anti-rheumatic drug (DMARDs) (joint lantern with inflammatory candle). Not as effective as MTX; usually used in refractory disease. o Adverse effects ▪ Myelosuppression & pancytopenia → immunosuppression (empty bone serving tray; immunocompromised cane on statue) ▪ Pancreatitis (pancreas sponge) ▪ Hepatotoxicity (both direct and d/t reactivation of latent infectious hepatitis) (liver spots) ▪ Inhibition of XO → increased 6-MP levels. Risk of adverse effects hugely increased with allopurinol or febustate coadministration (allopurinol nuns with purine beads) • Mycophenolate mofetil (Quasi-mofetil) o IMP dehydrogenase inhibitor, blocking GMP synthesis (knocking over grump statue) o Powerful anti-lymphoproliferative drug. Used in a variety of inflammatory and lymphoproliferative disorders (torn antibody lantern) o Adverse effects ▪ GI distress is common (queasy Quasimodo) ▪ Myelosuppression & pancytopenia → immunosuppression (empty bone serving tray; immunocompromised cane on statue) 1..3 anttiiin opplllaasstttiiiccs””:: cllaaad 1. 3 – ““N N Neeeo o lliiittth hiicc an nneeop ddrrriiib bbiiin nneee,, cyyt yta ttaar bbiiin nneee,, ggeeem m mccciiitttaaab b iin nnee arraaab • All are phosphorylated to triphosphate form, which can incorporate into DNA → breaks or blockage of synthesis & repair by blocking DNApol-α & DNApol-β (cracked replication fork demonstrating gene flow out of Africa; cracked glass). Cell cycle specific for S-phase (Stone phase) • All share the same limiting toxicity: Myelosuppression & pancytopenia → immunosuppression (broken bone spilling marrow; immunocompromised cane) • Cladribine (clad in bearskins) o Cytotoxic purine analog (purine-shaped club) o Resistant to adenosine deaminase → ↑↑ intracellular levels. o Indications ▪ Hairy cell leukemia (hairy caveman) ▪ CLL, NHL • Cytarabine (saber-toothed tiger) o Cytotoxic pyrimidine analog (hexagonal patterned fur) o Only active against hematologic malignancies, e.g. AML, non-Hodgkin lymphoma (scratched out antibody archers, crab, & Tcell swordsman) • Gemcitabine (gems inside geode) o Cytotoxic pyrimidine analog (hexagonal patterned fur) o Active against both hematologic malignancies and solid tumors (tumorous rocks, with crab not scratched out) 2..1 g Od Oddy C Iffoosffaaam 2. 1 – ““A A Alllk kky yllaaatt iin nng yssssseeey yy”””:: Cyc Cyyyccllo oop pph hho oosssp pph hhaam miiid ddeee,, Ifo m miiid ddeee,, B Bu ussu sul uulllfffaaan nn,, N Niittr tro r oossso oou uurrreeeaaass • Recall that an alkyl group is a molecular group with the formula -CnH2n+1. Alkylating agents add an alkyl group to nucleotide bases, most commonly to the guanine N7. This leads to the cross-linking of DNA strands, which causes DNA damage, interferes with DNA replication, and ultimately results in apoptosis. • Alkylating agents can act any point during the cell cycle. • Cyclophosphamide o The most commonly used alkylating agent (Cyclops Polyphemus). Like all of the alkylating agents, cross-links DNA (ankle chains). Once activated, forms a nitrogen mustard (similar to mustard gas). o Related agents are ifosfamide, melphalan, chlorambucil, mechlorethamine. o Activated by CYP450 in the liver (chariot with the CYP450 tag plate). o Indications ▪ variety of different cancers, both hematologic & solid tumors (sail torn through the image of a crab). ▪ Uniquely among the alkylating agents, used for autoimmune conditions (red lanterns look like immunoglobulins and are closer to the Cyclops than any of the other pharm avatars). o Toxicities ▪ Myelosuppression (bone club) ▪ An alternative metabolism pathway results in the toxic metabolite acrolein, responsible for several of the adverse effects of this drug ▪ Hemorrhagic cystitis caused by acrolein (red Greco-Roman fountain). Can preventatively administer mesna (“Maze”-na), the sulfhydryl group of which will bind acrolein and prevent the damage. ▪ ↑risk of bladder cancer (gold crab at the level of the bladder) ▪ SIADH & consequent hyponatremia (ADH bucket on cyclops head). Resultant encephalopathy in 10-30% of patients if not controlled. Worsened with hyperhydration during chemo, for unknown reasons. ▪ Infertility (M & F) & premature menopause (F) (dried up ovarian tree) ▪ Ifosfamide: Fanconi syndrome • Busulfan o Used for bone marrow ablation to prepare for BM transplant (beautiful sirens surrounded by cracked bones with bloody marrow exposed). Does not require bioactivation. o Toxicities ▪ Nigh universal severe myelosuppression (hence use as ablative) ▪ Lung toxicity, including acute ling injury, interstitial fibrosis, alveolar hemorrhage (sirens wearing golden chest plates with lung outlines) ▪ Hyperpigmentation – “busulfan tan” (dark-skinned sirens) • Nitrosoureas o include Carmustine, Lomustine, Streptozocin (mustang centaurs – sounds like -mustine; zebra striped centaur for streptozotocin). o Cross BBB, enabling treatment of CNS tumors including glioblastoma multiforme. o Toxicities ▪ CNS toxicities, including convulsions, dizziness, ataxia (centaur stumbling around clutching head) ▪ Myelosuppression ▪ Rarely, pulmonary fibrosis 2..2 Brrrea C sppllaatttiiin 2. 2 – “B reeeaaak kkfffaa sstt aatt Cis Ciiisssp pplllaaatttiiin n’s ’s”: s””:: Cisp nn,, ccaaarrrb bbo oop plla lat aatttiiin nn,, am miiifffo oossstttiiin nnee • Platinum-containing cancer chemo drugs include cisplatin, carboplatin, and oxaliplatin. All act by cross-linking DNA, similar to alkylating agents (double-helix chains with crossed links). Used to treat a variety of cancers, including solid tumors and hematologic malignancies (crumpled bag with a crab on it). • Toxicities: • Ototoxicity (gong-shaped earrings) results from targeting of outer hair cells in the Organ of Corti, causing a high frequency sensorineural hearing loss with tinnitus. Dose dependent. Cisplatin is notorious for this, although can also occur with high-dose carboplatin • Peripheral neuropathy in a stocking glove pattern (black arm gloves). Subacute neuropathy characterized by paresthesias and loss of sensation. Cisplatin > oxaliplatin >> carboplatin. • Nephrotoxicity & AKI, particularly with cisplatin (kidney shaped purse on Golightly’s flank). Can also cause acute tubular necrosis with muddy brown casts (muddy drainpipe). Two ways to prevent ATN o Amifostine, an organic thiophosphate, scavenges free radicals from cisplatin in the kidney (“Free Amethyst” sign over the visual of amethysts in a kidney-shaped purse) o Alternatively, IV saline diuresis (essentially induced polyuria) will flush toxic metabolites out of kidneys (cleaning the window with what appears to be a salt spray). • Myelosuppression, especially with cisplatin, and resulting immunosuppression (bone shaped box that has been depleted of its wares next to older woman with immunocompromised cane) 2..3 orru anntthr hrraaacc ycl ycclliin doox ubbiiiccciiin 2. 3 – ““D “Do D Do ox biiccciiin nn’s ’’s Looc ock cckkkeerr” r”: ””:: Blleeeo oom myyccciiin n, an ine nneeesss,, do xxo oorr ub n ox oru uub • Certain antibiotics have anti-tumor activity so are used on cancer treatment (cancer crab). • Bleomycin o Uses iron & oxygen to induce free-radical formation → breaks in the DNA strands (bleomycin beluga is holding a rust-colored crab and breathing out bubbles which are breaking the double helix of kelp). Acts primarily during G2 phase (Galleon). o Used to treat testicular cancer & Hodgkin’s lymphoma. o Adverse effects ▪ Inactivated in the body by bleomycin hydroxylase. Tissues with lower production of this enzyme, notably lungs and skin, have more toxic effects. ▪ Pulmonary fibrosis, pneumonitis, pulmonary infiltrates (lung-shaped coral) ▪ Skin hyperpigmentation, classically in a striated pattern termed “flagellate erythema” (hyperpigmented stripes on beluga) ▪ GI adverse effects (sea urchin being eaten in the background) ▪ Myelosuppression, although less so than some other anti-cancer agents (bone shaped chest is sitting empty and has been cleaned out of treasure) ▪ Alopecia (whales are pretty bald) • Anthracyclines o Most commonly used doxorubicin & daunorubicin; less commonly, idarubicin, epirubicin, & mitoxantrone (Santa Anthracycline was apparently a pirate ship; chests of rubies remind of the -rubicin suffix). o Several mechanisms interfere with cancer growth: ▪ 1) generate free radicals in the presence of NADPH, oxygen, and iron (bubbles rising from the treasure chest). ▪ 2) Intercalate into DNA, causing breaks in the DNA, inhibiting with replication and transcription (rubies have become incorporated into the double-helices of the kelp near the chest). ▪ 3) Interfere with the action of topoisomerase II, preventing repair of DNA. Used in the treatment of both solid tumors and hematologic malignancies. o Toxicities: ▪ Cardiotoxicity, most often a dilated cardiomyopathy → SHF with ↓LVEF (this is rarely seen at low doses) (dilated heartshaped sacks sit next to the ruby chest). • Prevented with dexrazoxane, an iron chelating agent (skeleton on deck is holding a non-dilated heart sack, waving a rusted iron razor; “deck razor” sounds a bit like dexrazoxane) ▪ Myelosuppression (empty bone-shaped chest sits on the deck of the ship) ▪ Alopecia (skeletons don’t have hair) ▪ Mucositis and stomatitis • Actinomycin D/dactinomycin o Intercalates in DNA, blocking RNA synthesis (artifacts from the ship have intercalated into the kelp helices). o Often used to treat pediatric malignancies, including Wilms tumor, Ewing’s sarcoma, rhabdomyosarcoma (the child-sized doll is sitting off to one side). o Toxicities are the usual: myelosuppression & alopecia (creepy bald doll). 2..4 2. 4 – ““U U Un nntttaaan nng ggllleeed d””:: To Top poiissso oom m meeerrraaasssee iin inh nnhhhiiib bbiiittto oorr s • Topoisomerase enzymes relieve the tension in DNA supercoils by nicking and re-ligating the DNA. Topoisomerase I nicks ssDNA and is involved in the process of DNA unwinding during replication, while topoisomerase II breaks and re-ligates dsDNA breaks. The topoisomerase inhibitors interfere with one of these steps and are used in cancer treatment (crab flag). • Inhibitors all specific to S-phase of the cell cycle, preventing movement to G2 (Rapunzel cannot descend the Stairs because they are broken and the witch is Gone 2 the forest). • Etoposide & teniposide o inhibit topoisomerase II →↑DNA degradation. (Rapunzel is climbing down the side of the tower on two-strand twists; but both strands have broken!) o Used in treatment of solid tumors, particular testicular and small cell lung cancer, as well as leukemias & lymphomas. o Toxicities: ▪ Myelosuppression and consequent immunosuppression (empty bone-shaped luggage. Witch with immunocompromised cane) ▪ Alopecia (Rapunzel is losing a lot of hair) • Topotecan and irinotecan o topoisomerase I inhibitors (man’s toucan sounds like -tecan. Man has a single-stranded ponytail rather than a double-stranded twist). o Used to treat ovarian and small cell lung cancers; irinotecan is used in colon cancer. o Toxicities ▪ Myelosuppression ▪ Severe and profuse diarrhea, some days after initiating treatment, d/t cell toxicity in GI tract (bird pooping). Can be so severe as to cause volume depletion. 2..5 Mee ttaaax crro 2. 5 – “M xxaaan nnee, Yo You u Chhri rriist issstttiinnee ””:: M Miicr ootttu uub bullee iin nnh hhiiib bbiiittto oorrrss • The taxols and the vinca alkaloids are all plant derived (yew and Vinca rosea, or periwinkle, respectively) and used in the treatment of cancer (forest setting; crab dinner). • Vinca alkaloids o bind β-tubulin, inhibiting polymerization into microtubules (woman – Cristine – is caught up in vines that look like metaphase spindles; the vines are breaking). This prevents mitotic spindle formation and results in M-phase arrest (monkey is swinging on vine, forming M shape). o Vincristine ▪ treats ALL, multiple myeloma, Hodgkin & non-Hodgkin lymphoma, and some pediatric tumors (Cristine). ▪ Toxicities: • Neurotoxicity, presenting with areflexia, peripheral neuritis and sensory neuropathy in a stocking glove pattern (Cristine is wearing stockings and gloves). Results d/t inhibition of axonal transport in the nerves. • Constipation and paralytic ileus (monkey with a plunger sitting on the outhouse) • Alopecia (bald monkey) o Vinblastine ▪ treat lymphomas and solid tumors (hunter blasting away with his gun). ▪ Toxicities • Myelosuppression (bones at the hunter’s feet). Note that this is not a side effect of vincristine. • Alopecia • Taxanes o hyper-stabilize β-tubulin in polymerized microtubules, arresting cells at the metaphase/anaphase transition (Tarzan is stabilized by a monkey holding his vine). o Used in breast and ovarian carcinomas, other solid tumors, small cell & non-small cell lung carcinomas. Are also a component of drug-eluting stents to prevent neointimal hyperplasia. o Toxicities: ▪ Hypersensitivity reactions are extremely common, in as many as 30% of patients. Can treat prophylactically with steroids, antihistamines. ▪ Alopecia ▪ Neurotoxicity, often presenting with burning paresthesias on extremities (Tarzan is holding Cristine’s glove) ▪ myelosuppression 3..1 errlllo unniiitttiiin 3. 1 – ““R R Rev Reeev uutttiiio oon nnaaarrry y K Kii nnaaasse iin nnh h iib bbiiittto oorrrsss”””:: im maaatttiiin niib ib, bb,, er ootttiinniiib bb,, sso oorrraaafffeeen nniiib bb,, sun nniiib bb,, vollu vveeem affeeen m mu uurraf nniiib b • Many cancers arise from kinase mutations → constitutive activation of proliferation signals, making these mutated kinases desirable targets for cancer therapy. • Many of the small molecule kinase inhibitors end in -nib (broken pen nib). Used to treat a variety of hematologic & solid malignancies (cracked crab bell). Tyrosine kinase inhibitors (i (inh nhibi bited tire re sw swing ng) g) • End in -tinib • Imatinib (imitating portrait of King George III) o Indications ▪ CML, characterized by increased levels of mature granulocytes, including eosinophils, neutrophils, basophils (colorful granules). Inhibits BCR-ABL fusion protein (“breakable” label) • BCR-ABL fusion protein results from t(9;22) – aka Philadelphia chromosome (hence the setting). The protein stimulates granulocytic precursors →CML. ▪ Blocks c-kit, found in GI stroma tumors (Congress Kit held by guy with beer belly & crab buttons) o Adverse effects ▪ Fluid retention → ankle & periorbital edema (king impersonator with baggy pantaloons) • Erlotinib (Earl of Tinib) o Blocks EGFR (Earl Geoffrey) ▪ Activation of EGFR → uncontrolled cell growth, metastasis, proliferation, angiogenesis. overexpressed in several solid tumors including non-small cell lung CA, pancreatic CA (crab on lung shaped lapel) o Adverse events ▪ Cutaneous involvement common, d/t EGFR expression in the skin. Classically papulopustular acneiform rash (Earl’s spotty rash) ▪ Diarrhea (muddy pants). Not usually severe. • Sunitinib (rising sun), Sorafenib (soaring eagle) o Inhibit multiple Y-kinases, including VEGF receptors – angiogenic growth factor . Result in blocking vasculogenesis needed for primary & metastatic tumors (hoeing up vegetables) o Indications: ▪ Sorafenib: RCC (flank crab suspender buckles), HCC ▪ Sunitinib: RCC (flank crab suspender buckles), GIST o Adverse effects ▪ Cutaneous effects including hyperkeratosis & rashes (farmer’s hyperkeratotic callouses & sunburn) ▪ ↑risk of hemorrhage, d/t disruption of VEGF-R on the vascular endothelium (farmer bleeding) • Vemurafenib (venomous snake) o -rafinib for B-Raf inhibit (B. FRA signature inhibited by broken nib). ▪ BRAF is a protein kinase involved in activation of melanocyte proliferation. V600E (valine → glutamic acid) seen in 4060% of patients with melanoma – hence vemu- for V→E mutated BRAF inhibitor. o Treats V600E BRAF positive malignant melanoma (disseminated ink). Improved survival & long-term events 3..2 Thhee M R ux iim 3. 2 – “Th MA A AB B w wh ho w wo oou uulld bbee kkiiin nng g ””:: Rit Riittu uux xxiiim m maaab bb,, cceeettux m maaab bb,, bbeeev vvaaciizzzu uum m maaab bb,, aallleeem m mtttu uuzzzu uum m maa b, ttrrraaassstttu uuzzzu uum m maaab b • Antibodies used in treatment of B-cell lines, created by a single cell line, hence monoclonal Ab. -mab = monoclonal Ab; -ximab = chimeric Ab – human derived + mouse derived variable region; -zumab = humanized Ab. • Rituximab (coronation ritual) o Chimeric Ab targeting CD20 (chimera sigil; XX straps). Results in in depleting B-cells and increases cellular killing via targeting for killing. o Indications ▪ CD20 ⊕ hon-Hodgkin lymphomas ▪ CLL (abnormal proliferation of abnormal B-cells & T-cells) (chronically worn tapestry with B-cell archers & T-cell knights) ▪ Disease modifying anti-rheumatic drug (DMARDs) (joint lantern with inflammatory candle). Usually in combination with MTX for treatment-resistant RA. ▪ Immunosuppressive therapy, including for granulomatosis with polyangiitis, microscopic polyangiitis (torn Ab lantern) o Adverse effects ▪ Immunosuppression (bishop’s cane). Not as much as one might expect, as Ig levels generally stay fairly normal. May see immunosuppression d/t neutropenia ▪ Hep B reactivation ▪ Rarely associated with progressive multifocal leukoencephalopathy, from the JC virus (laurel leaves) ▪ Infusion reaction common in 50% of patient. Presents headache, fever, rash, puritis, dyspnea, hypotension (swollen pink cherub with ivy). Thought to be d/t Ag-Ab interaction → activation of immune cells • Managed with antihistamines, acetaminophen, NSAIDS ▪ Serum sickness – type III HS reaction, resulting from tissue deposition of circulating immune complexes, causing fever, rash, arthralgia, proteinuria, LAD within 7-10 days (Delayed onset poisoning) • Occurs d/t targeting of non-human Ab components • Cetuximab (elephant tusks) o Binds EGFR (giraffe). EGFR acts via a tyrosine kinase. o Adverse effects ▪ Infusion reaction common in 50% of patients e.g. headache, fever, rash, puritis, dyspnea, hypotension (swollen pink cherub with ivy). Thought to be d/t Ag-Ab interaction → activation of immune cells • Managed with antihistamines, acetaminophen, NSAIDS ▪ Serum sickness – type III HS reaction, resulting from tissue deposition of circulating immune complexes, causing fever, rash, arthralgia, proteinuria, LAD within 7-10 days (Delayed onset poisoning) • Less common than in rituximab • Bevacizumab (beverage lady) o VEGF inhibitor by binding directly to VEGF (chopped vegetables). Anti-angiogenic (chopped vascular vegetables) o Useful for treating certain metastatic cancers (Cracked crabs) o Used for wet macular degeneration, characterized by retinal hypoxia → subretinal VEGF production → angiogenesis (pillow with macular wet spot) o Adverse effects ▪ Bleeding, sometimes serious and even fatal (bloody aprons) ▪ ↑thromboembolic events (clot cubes) ▪ GI perforation (perforated sack of vegetables). Most commonly in metastatic CRC, epithelial ovarian CA. • Alemtuzumab (Alms) o IgG monoclonal Ab that binds CD52 found on normal & malignant cells of lymphoid lineage (natural killer cells, B & T cells). Initiates direct cytotoxicity by recruitment of complement. (Alms-seeker is begging from archer and knight; 52 design etched on knight’s scabbard) o Used in treatment of CLL (chronically worn tapestry with B-cell archers & T-cell knights) o Adverse events ▪ Marrow suppression, increased risk of AI disorders, infection risk • Trastuzumab (tapestry weaver) o Monoclonal antibody against HER2/neu ⊕, a Y-kinase (tire swing with her 2 babies). Inhibits MAPK & PI3K/AKT signaling pathways, & facilitates antibody mediated destruction tumor cells. ▪ HER2 ⊕ seen in 20% of breast CA (crab bra), as well as adenocarcinomas of the ovary, lungs, stomach, salivary glands. o Adverse effects ▪ Cardiotoxicity (unraveling heart tapestry). Presents most often as ↓LVEF, less commonly as HF. Generally resolves with cessation of treatment.