Alkylating agent (transfers alkyl group to DNA causing ss/ds DNA crosslinks → miscoding, strand breakage via guanine excision, and G2 cell cycle block); Lymphopenic effects B cells >> T cells;

Prodrug*, converted into active Aldophosphamide;

 Metablized by CYP2B*

Anti-cancer and immunosuppressive agent (can be used pre-stem cell transplant and in severe/refractory RA);

SE - Pancytopenia limits dosages*,

Renal failure, urotoxicity (hemorrhagic cystitis, damage due to acrolein production, Tx w hydration and MESNA), Pulmonary fibrosis,

Significant N/V,

Menstrual irreg, Cat D in pregnancy, avoid in lactation;

*Note that all alkylating agents produce pulm fibrosis but that this effect is pronouced here. Will not be incl as SE on other alkylating agent cards.

Alkylating agent (see mech specs w Cyclophosphamide);

Anticancer drug;

SE - Renal failure, Urotoxicity (damage due to acrolein production, tx: w hydration+MESNA), CNS Toxicity* (altered mental status, coma, seizure, ataxia)

Alkylating agent

In the same category as Cyclophosphamide and Ifosfamide

SE: Significant N/V

(not discussed otherwise but on the drug list)

Alkylating agent;

Oral or IV, hepatic metabolism;

Hydrolized to produce its active product (methylsulfanes);

Anticancer drug and Immunosuppressant (given with Cyclophosphamide pre-stem cell transplant).

SE - Addison-like syndrome (adrenal insufficiency), Hepatoxic (Veno-occlusive liver dz), Ulcers, myelosuppression, lung fibrosis

Alkylating agent

Parenteral admin;

Extensive Hepatic metabolism (see tox);

Highly lipophilic (enters CNS)→ tx brain tumors;

MoAs: 1. Alkylates O6-guanine→DNA breakage;

2. Decomposition metabolite also inhbits DNA repair;

SE: Injection site rxn, CNS toxicity (seizures), delayed pulmonary fibrosis, Hepatic Toxicity (↑ transaminases and alk phos + hyperbilirubinemia +Veno-Occlusive Dz*, tx: Defibrotide), high incidience of N/V

Alkylating agent,

Lipophylic, enters the CNS (tx brain tumors);

Oral admin;

Hepatic metabolism (but tox not as severe as BCNU);

SE: Delayed pulmoanry fibrosis, CNS toxicity (encephalopathy, seizures, dementia), Hepatotoxicity (↑ transaminases/alk phos, hyperbilirubinemia, not veno-occlusive dz).

Alkylating agent;

Rapidly hydrolyzed to TEPA → forms interstrand DNA cross-links;

Admin IV, IVe or IC;

SE - Neurotoxic (seizures, dementia, coma), Myelosuppression,

If given IVe: Local toxicity (dysuria, urinary urgency/retention, cystitis, general bladder tox)

Alkylating agent - Abx;

Metabolically activated under reducing conditions;

Alkylates and generates free radicals;

SE: Myelosuppression (w/ slow recovery), Injection site rxns, Hemolytic anemia (caused by endothelial damage)

Alkylating agent→Intrastrand DNA links, primarily at N7-guanine (forming G-A crosslinks)*;

IV only (all -platins are IV only);

SE - Ototoxic (tinnitus and high-freq loss),

Nephrotoxic (tx w hydration, Cl diuresis and the cytoprotective agent Amifostine),

Significant N/V,

Progressive Neuropathy (peripheral: motor & sensory),

2° malignancy (AML)

Alkylating agent→Intrastrand DNA links, primarily at N7-guanine (forming G-A crosslinks)*;

IV only;

SE - Less ototoxic, nephrotoxic, N/V-inducing, and neurotoxic than Cisplatin,

Myelosuppression is limiting*

Methylating agent;

Metabolically activated;

IV only;

SE: Significant N/V and Flu-like symptoms

Methylating agent (causes chromatid breaks and translocations);

Prodrug, activated in liver by CYP;

Resistance develops rapidly when used alone;

SE: Weak MAOI, causes Disulfriam (Antabuse)-like rxns

Interactions: Avoid with other MAOIs and Alcohol (causes GI upset and malaise)

Antimetabolite (Folic Acid Analog), Immunosuppressant - Cell Cycle Inhibitor and DMARD;

Depletes cofactors, Inhibits DHFR & thymidylate synthase (TS);

Is polyglutamated in metabolism and these PG products also inhibits TS;

S-phase-specific Cell cycle inhibition;

Polyglutamation activates MTX but this form can't leave the cell;

SE: GI toxicity (mucositis, esophagitis), BM hemorrhage, Renal and hepatic (↑ enzymes) toxicity, Pneumonitis; (Rescue w/ Leucovorin [Folinic acid]), Teratogen (Cat X in pregnancy, avoid also in lactation)

Antimetabolite (Folic Acid Analog);

Strongly inhibits GART (thereby inhibiting prine biosynthesis);

Tx mesothelioma

Antimetabolite (Pyrimidine analog);

Inhibits thymidylate synthase - req "triple complex," actions enhanced by Leucovorin;

IV admin;

SE - Angina (cardiac ishchemia), Myelosuppression, Hand-Foot Syndrome (erythema, desquamation, pain/sensitivity)

Antimetabolite agent (Pyrimidine analog);

Inhibits base stacking = no chain elongation;

Prodrug, converted to ARA-CTP (required for action); S phase specific cell cycle arrest;

SE - POTENT myelosuppression, noncardiogeneic pulmonary edema, Hand-Foot Syndrome

Antimetabolite agent (Pyrimidine analog);

Locks cell division (not S phase specific);

SE - myelosupp, FLU-Like Syndrome, ↑ liver transaminases, interstitial pneumonitis

Antimetabolite agent (Pyrimidine analog);

Oral precursor of 5-FU;

SE - Hand-Foot Syndrome (erythema, pain etc...) is more common* than with 5-FU

Antimetabolite agent (Purine analog);

Oral admin w/ pharmacogenetic dosing*;

Resistance @ HGPRT, alkaline phosphatase;

SE - myelo (slow onset), ↑ hepatic enzymes;

Interactons: Allopurinol blocks metabolism of 6-MP by XO (do not give together, causes 6-MP toxicity).

Antimetabolite (Purine analog);

Inhibits adenosine deaminase → ↓ dATP → B and T cell apoptosis;

Parenteral admin;

SE: Myelosuppression is dose-limiting*

Antimetabolite (Purine analog);

Prodrug metabolized/phosphorylated in the cell to an active triphosphate that inhbits DNA synth and ribonucleotide reductase;

Oral admin;

Active against indolent cancers*;

SE : Lingering immunosuppression (> 1yr)

Antimetabolite (Purine analog);

Prodrug metabolized/phosphorylated in the cell to an active triphosphate that inhbits DNA synth and ribonucleotide reductase;

Oral admin;

Active against indolent cancers*;

SE : Myelosuppression

Antimetabolite (Purine analog); Similar to 6-MP;

Metabolized by HGPRT;

Oral admin;

No allopurinol interaction*

Vinca alkaloid; Binds β-tubulin, preventing polymerization→metaphase arrest;

Resistance: P-glycoprotein, mutation of the β-tubulin binding site;

SE: Neurotoxicity (MT int he CNS!), Leukopenia, Alopecia, local cellulitis (if extravasated), ↓ DTR/motor/sensation

Vinca alkaloid; Binds β-tubulin, preventing polymerization→metaphase arrest;

Resistance: P-glycoprotein, mutation of the β-tubulin binding site;

SE: Cumulative Neurotoxicity (MT int he CNS!), Alopecia, local cellulitis (if extravasated), ↓ DTR/motor/sensation + numbness and tingling;

NO LEUKOPENIA

Vinca alkaloid; Binds β-tubulin, preventing polymerization→metaphase arrest;

SE: Neurotoxicity, Leukopenia, Alopecia, local cellulitis (if extravasated), ↓ DTR/motor/sensation

 Stabilizes DNA Topoisomerase-1 cleavable complex→ss/ds breaks;

Resistance: change in Topo-1or2;

Hepatic metabolism;

SE: Neutropenia, diarrhea, N/V, ↑ hepatic enzymes;

CI - Gilbert Syndrome (severe toxicity)

 Stabilizes DNA Topoisomerase-1 cleavable complex→ss/ds breaks;

Resistance: change in Topo-1or2;

Hepatic metabolism;

SE: Neutropenia, Dose-limiting diarrhea*, N/V, ↑ hepatic enzymes, ACH-ase Inhibition;

CI - Gilbert Syndrome (severe toxicity)

Complexes with DNA Topoisomerase-II → prevents resealing of DNA breaks;

Oral;

SE - myelosuppression, alopecia

Complexes with DNA Topoisomerase-II → prevents resealing of DNA breaks;

IV admin, extensive hepatic metabolism;

SE - myelosuppression, N/V

Taxane [Taxol];

Binds and prevents depolymerization of β-tubulin

→mitotic arrest;

Needs surfactant for solubility;

 CYP metabolism;

SE - +Cremaphor=Hypersensitivity,

Stocking Glove Sensory Neuropathy, BM depression, myalgias, mucositis

Taxane, more potent, lower risk of hypersensitivity rxn and fewer surfactant issues than Paclitaxel;

Binds and prevents depolymerization of β-tubulin

→mitotic arrest;

CYP metabolism;

SE: Neutropenia (severe but short in duration) Progressive Edema (tx: dexamethasone)

Anthracycline;

Multiple MoA: Intercalates DNA, Inhibits Topoisomerase-II, Generates free radicals

(all MoA help induce apoptosis);

SE - Myelo, Alopecia, extravasational necrosis, Cardiotoxicity (reversible tachy, arrhythmia, ↓ Ef, release of troponin, T; Irreversible CHF), Significant N/V, red urine;

Give with Dexroxazone (Fe chelator: ↓ cardiotoxicity)

Anthracycline;

Multiple MoA: Intercalates DNA, Inhibits Topoisomerase-II, Generates free radicals

(all MoA help induce apoptosis);

SE - Myelo, Alopecia, extravasational necrosis, Cardiotoxicity (reversible tachy, arrhythmia, ↓ Ef, release of troponin, T; Irreversible CHF), red urine;

Give with Dexroxazone (Fe chelator: ↓ cardiotoxicity)

Anthracycline;

Multiple MoA: Intercalates DNA, Inhibits Topoisomerase-II, Generates free radicals

(all MoA help induce apoptosis);

SE - Myelo, Alopecia, extravasational necrosis, Cardiotoxicity (Less cardio tox than others in this class*), red urine;

Can still give with Dexroxazone (Fe chelator: ↓ cardiotoxicity)

Anthracycline;

Multiple MoA: Intercalates DNA, Inhibits Topoisomerase-II, Generates free radicals

(all MoA help induce apoptosis);

SE - Myelo, Alopecia, extravasational necrosis, Cardiotoxicity (reversible tachy, arrhythmia, ↓ Ef, release of troponin, T; Irreversible CHF), red urine

"N

Anthracycline;

Multiple MoA: Intercalates DNA, Inhibits Topoisomerase-II, Generates free radicals

(all MoA help induce apoptosis);

SE - Myelo, Alopecia, extravasational necrosis, Cardiotoxicity (reversible tachy, arrhythmia, ↓ Ef, release of troponin, T; Irreversible CHF), red urine

Related to Anthracyclines;

Intercalates DNA & Inhibits Topoisomerase-II→DNA strand breaks;

IV admin;

SE - Myelo, Alopecia, stomatitis, Cardiotoxicity, Blue urine, discoloration of the nails

Complexes w/ Fe, compex oxidizes the deoxyribose of thymidylate and other nucleotides→DNA breaks (similar to the effects of Topo block);

IV or IM admin;

SE: Pulmonary toxicity (dry cough, fibrosis), cutaneous toxicity (hyperpigmentation, hyperkeratosis)

Actinomycin;

Intercalates DNA (adjacent G-C pairs) → ssDNA breaks, generates free radicals, has topo-II action;

IV admin;

SE - pancytopenia, anorexia, N/V, diarrhea, alopecia, extravasational necrosis, Skin toxicity (erythema, desquamation, inflammation and pigmentation, esp when skin also exposed to X-rays)

Hydrolyzes asparigine which ↓ protein synthesis in leukemic cells;

SE - Pancreatitis (necrotic/inflammatory), potentially fatal hypersensitivity rxn, immune suppression hyperglycemia, clotting issues, hypoalbuminemia, intracranial hemorrage.

Free radical scavenger, scavenges the essential cofactor of ribonucleotide reductase→impaired DNA synthesis;

Oral admin;

Used as a myelosuppressive to tx myeloproliferative syndromes;

SE: Myelosuppression, desquamative interstitial pneumonitis, hematopoietic depression, GI

4 chief MoA: Inhibition of tumor cell proliferation, Inhibition of tumor cell adhesion to stroma, Inhibition of angiogenesis, Enhanced NK cell activation;

SE - sedation, constipation, peripheral sensory neuropathy

Retinoic Acid derivative [Retin-A];

Promotes diff/maturation of WBCs and disrupts repressive fusion gene being overexpressed in APL;

Tx: APL (acute promyelocytic leukemia, a type of AML);

SE - Retinoic Acid Syndrome (fever, dyspnea, weight gain, pleural or pericardial effusions), ↑ liver enzymes, cheilitis, dry skin, hyperlipidemia, teratogen*

Anti-inflammatory + immunosuppressive;

Used to tx ALL, malignant lymphoma, CLL, NHL, and Multiple Myelomas;

Oral admin;

SE - Cushingoid Syndrome

Blocks VEGF;

Anti-angiogenic; Limits growth of tumor by limiting its ability to generate its own blood supply;

SE - HTN*, CHF, pulm hemorrhage, GI perforation

[Herceptin]

Binds EGFR-2, HER-2/NEU→Apoptosis, ADCC;

Tx breast cancer;

SE - Cardiomyopathy, infusion toxicity

Binds EGFR-1, HER-1→Apoptosis, ADCC;

Tx colorectal cancer;

SE: Infusion rxn, rash with sun exposure

Binds EGFR-1, HER-1→Apoptosis, ADCC;

Tx colorectal cancer;

SE: Infusion rxn, rash with sun exposure

Binds CD-20 - B-cell depletion;

Binds and dimerizes w/ cell surface receptors (apop); Provides target for classical complement activation (C1q); Provides target for macrophages;

Tx: Cancer and RA;

SE - lymphopenia, infusion rxn

Binds CD-20 - B-cell depletion;

Stable binding, effective against low levels of CD-20 expression;

Tx: CLL

SE - neutropenia, Progressive multifocal leukoencephalopathy*

Binds CD-52 (present on B, T, NK, macrophages, platelets, and male reproductive cells), causes lysis of T > B cells and cell depletion;

Tx: CLL, prep for stem cell transplant;

SE - Infusion rxns (chills, rigors, N/V), profound and long lasting lymphopenia

Binds CD-20 - B-cell depletion;

Apoptosis, weak phatocytosis;

Tx: NHL;

SE: Sustained lymphopenia*

Binds CD-20 - B-cell depletion;

Tx: NHL, prep for stem cell transplant;

SE - bone marrow suppression, hypothyroidism

EGFR-TK inhibitor;

Prevents EGFR-TK from phosphorylating, blocks signal transduction;

Rapid resistance via expansion of clones w/ mutated target;

SE - fatigue, rash, N/V/D, anorexia

EGFR-TK inhibitor;

Prevents EGFR-TK from phosphorylating, blocks signal transduction;

Rapid resistance via expansion of clones w/ mutated target;

SE - fatigue, rash, N/V/D, anorexia

EGFR-TK inhibitor;

Targets EGFR (HER-1,2);

Tx: Breast cancer;

SE - hepatotoxic, cardiotoxic (↓ LVEF and prolongs QT), N/V/D, rash

BCR-ABL-TK inhibitor [Gleevic];

Targets BCR-ABL;

Oral admin;

High lvls of resistance;

SE - cytopenia, N/V/D, edema, muscle cramps, fatigue, rash

BCR-ABL TK inhibitor; Targets BCR-ABL;

Oral admin;

SE - cytopenia, N/V/D, edema, muscle cramps, fatigue, rash

BCR-ABL TK inhibitor;

Targets BCR-ABL, Increased potency;

SE - pancytopenia, QT prolongation, ↑ serum lipase, N/V/D, edema, rash, abdominal pain

VEGF TK inhibitor;

Multi-inhibitor incl VEGFR, PDGFR, KIT, FLT;

Tx: Renal Cell, GIST;

SE: Cardiotoxicity (↓LEVF, prolonged QT, CHF), ↑ hepatic enzymes, lymphopenia, thrombocytopenia, graying of hair and skin

VEGF-TK inhibitor;

Multi-inhibitor incl VEGFR, PDGFR, KIT, FLT;

Tx: Renal Cell and Hepatocellular Carcinomas;

SE: Hand-Foot Syndrome, cytopenia, diarrhea, ↑ bleeding risk

VEGF-TK inhibitor;

Multi-inhibitor incl VEGFR, PDGFR, KIT, FLT;

Tx: Renal Cell Carcinoma;

SE: ↑ hepatic enzymes, HTN, prolonged QT interval, hypothyroidism, ↑ bleeding

Proteosome inhibitor;

Inhibits the UQ-proteosome pathway; Prevents degradation of IkBa, activates caspases, inhibits binding of myeloma cell to stroma, ↓ angiogenesis, inhibits cytokine interactions;

Tx: Multiple myeloma, NHL;

SE - thrombocytopenia, peripheral neuropathy, dizziness, paresthesias, N/V/D, fever, arthralgia

Mimics endogenous INF - anti-viral, anti-neoplastic;

Cell cycle arrest in Go, apoptosis, ↑ cellular immunologic response;

CYP Inhibitor;

Tx: CML, hairy cell leukemia, melanoma, bladder and ovarian

SE: Neuropsychiatric, flu-like symptoms

Immunosuppressant - mTOR inhibitor;

Binds FKBP12, inhbitis activation of mTOR → inhibition of 2nd phase of activation (signal tranduction/prolif of T cells), ↓ synthesis of proteins for nutrient uptake, angiogenesis, ribosome biogenesis, cell growth and proliferation → G1 arrest;

Tx: Renal Cell Carcinoma

SE: Dose-dependant Hyperlipidiemia, Azotemia, Thromboembolism, HTN, Hepatotoxicity (incl fatal hepatic necrosis)

mTOR inhibitor;

↓ synthesis of proteins needed for nutrient uptake, angiogenesis, ribosome biogenesis, cell growth and proliferation;

Tx: Renal Cell Carcinoma

mTOR inhibitor;

↓ synthesis of proteins needed for nutrient uptake, angiogenesis, ribosome biogenesis, cell growth and proliferation;

Tx: Renal Cell Carcinoma

Hormone-ish;

GnRH agonist, hyperstimulation leads to desenitization and "castration" of testosterone levels;

Avoid the initial flare by giving AR blocker;

SC or IM admin;

SE - sweat, ↓ libido, hot flashes, nausea, ↓ bone and muscle mass

Hormone-ish;

GnRH agonist, hyperstimulation leads to desenitization and "castration" of testosterone levels;

Avoid the initial flare by giving AR blocker;

SC or IM admin;

SE - sweat, ↓ libido, hot flashes, nausea, ↓ bone and muscle mass

Hormone-ish - AR blocker;

Inhibits androgen binding, reflex ↑ levels of testosterone and androgens;

Oral admin;

SE - gynecomastia, vasomotor flushing, mastodynia, reduced libido

Hormone-ish - AR blocker;

Inhibits androgen binding, reflex ↑ levels of testosterone and androgens;

Oral admin;

SE - gynecomastia, vasomotor flushing, mastodynia, reduced libido

SERD - hormone-ish;

Completely suppresses estrogen receptor expression;

IM admin allows montly dosing and sustained plasma drug levels;

Resistance - ↑ growth factor signals;

SE - nausea, asthenia, vasodilation

SERM - hormone-ish;

Estrogen agonist at bone (↑ density); Estrogen antagonist at mammary glands; ↓ cholesterol;

Oral admin;

SE - endometrial hypertrophy (cancer risk), Thromboembolitic dz (DVT/CVA risk), retinal degeneration (at high doses)

SERM - hormone-ish;

Estrogen agonist at bone (↑ density); Estrogen antagonist at mammary glands; ↓ cholesterol;

Oral admin;

SE - endometrial hypertrophy (cancer risk), Thromboembolitic dz (DVT/CVA risk), retinal degeneration (at high doses)

Aromatase Inhibitor - aromatase is involved in the conversino of androgens to estrogens in periphery;

Non-steroidal - competitive, reversible inhibition, Steroidal - irreversible inhibition;

Oral admin;

SE - arthralgia, diarrhea, nausea, hot flashes

Aromatase Inhibitor - aromatase is involved in the conversino of androgens to estrogens in periphery;

Non-steroidal - competitive, reversible inhibition, Steroidal - irreversible inhibition;

Oral admin;

SE - arthralgia, diarrhea, nausea, hot flashes

Aromatase Inhibitor - aromatase is involved in the conversino of androgens to estrogens in periphery;

Non-steroidal - competitive, reversible inhibition, Steroidal - irreversible inhibition;

Oral admin;

SE - arthralgia, diarrhea, nausea, hot flashes

Hormone-ish; Alkylating agent that targets cells w/ estrogen receptors; Binds MT promoting disassembly; DNA breakage, apoptosis, arrest of cell cycle at G2/M;

SE - N/V/D, gynecomastia, mastalgia

What is TLS?

Who gets it?

How do you treat it?

TLS: Tumor Lysis Syndrome is a metabolic complication of cancer treatment whose sx are caused by the breakdown products of tumor cells (purine nucleic aids, K+ and P).

Seen in ALL, Burkitt's Lymphoma, Non-Hodgkin's Lymphoma, and solid tumors w/ high proliferaton rates.

Tumor cell breakdown products are renally eliminated and effectively jam up/saturate the renal system.

Producing ↑ levels of K+ and P and ↓ levels of Ca2+.

Causes Gout!

Tx: Hydration, correction of A/B imbalance with sodium bicarb to alkalinize the urine, Allopurinol to prevent uric acid formation, and Rasburicase to degrade uric acid to water-soluble allantoin.

Actinomycin;

Intercalates DNA (adjacent G-C pairs) → ssDNA breaks, generates free radicals, has topo-II action;

IV admin;

SE - pancytopenia, anorexia, N/V, diarrhea, alopecia, extravasational necrosis, Skin toxicity (erythema, desquamation, inflammation and pigmentation, esp when skin also exposed to X-rays)

Polyclonal anthithymocyte globulins;

Bind non-specifically to T cells→Fc-mediated phagocytosis/complement lysis of T-cells;

IV admin;

Tx: Aplastic anemia and in marrow and organ transplantation;

SE: Production of horse/rabbit Ig neutralizing Abs, Fever/chills, HypoT, thrombocytopenia

Immune Globulin;

Immunosuppressant;

IV admin

Immunosuppressant;

anti-CD3 (on CD3+,4+,8+ T cells) Ab;

Causes reversible depletion of T cells;

SE: Formation of human-mouse neutralizing Abs, Acute hypersensitivity rxn, Fever (MC), chills, dyspnea, angina, tremor, HA, wheezing, rigor, HTN;

Pretreatment with corticosteroids.

Calcineurin Inhbitor;

Inhbits the first phase of T-cell activation (downstream inhibition of the gene products for T (IL2, IFNγ) and B (IL4) cell activation;

SE: Dose/duration-dependant Nephrotoxicity* (renal vasoconstriction, ↑ creatinine, BUN, K+, BP, difficult to tell this toxicity from graft rejection), Hirsutism/hypertrichosis (hairy!),

Gingivial Hyperplasia*,

Pregnancy Cat D, do not use during lactation

Calcineurin Inhbitor;

Inhbits the first phase of T-cell activation (downstream inhibition of the gene products for T (IL2, IFNγ) and B (IL4) cell activation;

100x more potent than Cyclosporine at T cell suppression;

SE: Dose/duration-dependant Nephrotoxicity* (renal vasoconstriction, ↑ creatinine, BUN, K+, BP), Neurotoxicity; Pregnancy Cat D, not for use during lactation

Calcineurin Inhbitor;

Inhbits the first phase of T-cell activation (downstream inhibition of the gene products for T (IL2, IFNγ) and B (IL4) cell activation;

SE: Dose/duration-dependant Nephrotoxicity* (renal vasoconstriction, ↑ creatinine, BUN, K+, BP, difficult to tell this toxicity from graft rejection)

Immunosuppressant, anti-inflammatory corticosteroid; Nuclear transcription inhibitor (?);

Neutrophilia (↑ #PMN), Eosino/myocyto/lymphopenia;

SE with prolonged use: Myopathy, impoaried wound healing, soteoporosis, avascular necrosis, ↑ susceptibility to invection/reactivation of TP, Cushings Syndrome (HTN, hypercholestrolemia, hyperglycemia)

Immunosuppressant - CD-25 Receptor Blocker;

Blocks IL-2Rα, expressed on the surface of activated T-cells→impaired response to antigenic challenge;

No change in lymphocyte numbers, no ↑ risk of secondary malignancy;

Long t_1/2;

SE: GI toxicity (MC), acute hypersensitivity rxns

Immunosuppressant - CD-25 Receptor Blocker;

Blocks IL-2Rα, expressed on the surface of activated T-cells→impaired response to antigenic challenge;

No change in lymphocyte numbers, no ↑ risk of secondary malignancy;

Long t_1/2;

SE: GI toxicity (MC), acute hypersensitivity rxns

Immunosuppressant - Cell Cycle Disruptor;

Inhibits activated T-cell proliferation, blocks 2° Ab responses by memory B cells;

Advantages: effects are seleftive on lymphocytes, no chromosomal breaks;

SE: GI tox (MC, Constipation, dyspepsia, N/V/D)

Immunosuppressant - Cell Cycle Disruptor;

Purine analog;

SE: Category D in pregnancy (should be avoided entirely in lactation), Myelosuppression, GI toxicity, ↑ risk of skin cancer;

Interactions: Allopurinol and 5-aminosalicylates  ↑ toxicity of azathioprine,

Azathioprine ↓ efficacy of warfarin (causes ↑ INRs),

Immunosuppressant - Co-stimulator blocker;

CTLA4 fusion protein, blocks engagement of CD28 preventing T cell costimulatory signal → ↓ T cell proliferation (fewer cytokines, TNFa, IFNg, IL2 etc...);

SE: HA, dizziness, HTN, 2° lung malingnancy, RA

Immunosuppressant - Co-stimulator blocker;

CTLA4 fusion protein, blocks engagement of CD28 preventing T cell costimulatory signal → ↓ T cell proliferation (fewer cytokines, TNFa, IFNg, IL2 etc...);

SE: HA, dizziness, HTN, 2° lung malingnancy, RA

Immunosuppressant - Co-stimulator blocker;

Binds the alpha subunit of the LFA-1 preventing its binding to intercellular adhesion molecule-1 (ICAM1) → ↓ inflammation and rejection, prevents binding of T cells to endothelial cells and T cell migration;

Tx: SC injection for psoriasis;

SC: 1st dose rxn, pain, flu-like symptoms, URI, 2° malignancies (skin, solid tumors)

Immunosuppressant - Co-stimulator blocker;

Binds LFA-3 preventing its interaction with CD-2 on T-cells thereby selectively blocking the costimulation of CD2+ memory T-cells*;

Simultaneous binding of IgG1 to IG receptors on cytotoxic cells + LFA3 to CD2 on T cells induces apoptosis;

Tx: IM for psoriasis;

SE: Lymphopenia, 2° skin cancer, hypersensitivity rxns