Block 4 Module 2 Drugs/MISC.

warfarin

vitamin K antagonist that will ↓ levels of all vitamin K-dependent factors (II, VII, IX, X); works by inhibiting epoxide reductase (normally reduces vitamin K to active, reduced form), keeping vitamin K in OXIDIZED form --- oxidized Vitamin K is unable to make more activated clotting factors; this drug takes several days to achieve effects (time required for the clotting factors to fall), which is why it is co-administered (not always) with heparin (acute agent); used for stroke and atrial fibrillation prevention, mechanical heart valves, DVT/PE; dose adjusted to reach target PT/INR --- PT test most sensitive bc Factor VII has shortest half-life (first to fall after this drug administration); HEPARIN provides anticoagulation (acute) during initiation of this therapy; adverse effects = mainly bleeding, skin necrosis (thrombosis of skin tissue, 2° to protein C deficiency) AVOIDED DURING PREGNANCY!! -- crosses the placenta, potential for abnormal fetal development (UFH used instead) NOTE: in first few days of therapy, there is potential for brief, prothombotic period: protein C levels to fall (also vitamin K dependent), which is a pro-thrombotic signal (which is why heparin therapy is begun during the initiation of this tx to offset the prothrombotic effects) NOTE: dose of this drug required to reach a given INR may need to be REDUCED in individuals with polymorphisms in the gene that encodes vitamin K epoxide reductase complex (VKORC1)*** [thus, may need genetic testing to aid in calibrating the correct dosage] NOTE: OD of this drug can be treated with FFP (rapid reversal) or vitamin K1 (non-rapid reversal)

vitamin K (AKA vitamin K1 = phytonadione)

vitamin that is required for the synthesis of four different clotting factors, including prothrombin (II) & factors VII, IX & X, as well as the endogenous anticoagulant proteins C and S; usually given as subQ or IM injection (if have to do IV route, must administer it SLOWLY) and is indicated for tx of anticoagulant-induced prothrombin (factor II) deficiency caused by coumarin or indanedione derivatives, prophylaxis and therapy of hemorrhagic disease of the newborn, factor II (prothrombin) deficiency due to antibacterial therapy or 2° to factors limiting its absorption/synthesis, inc. obstructive jaundice, biliary fistula, sprue, ulcerative colitis, celiac disease, intestinal resection, CF of the pancreas, and regional enteritis, or other drug-induced hypoprothrombinemia that is undoubtedly the result of interference with its metabolism (i.e. salicylates); contraindicated in pt with known HYPERSENSITIVITY; adverse effects = severe rxns, inc. hypersensitivity, anaphylaxis, and fatalities, have occurred when it is given via IV; therefore, IV route should be restricted to those situations where other routes are not feasible and the serious risk involved is considered justified*** NOTE: warfarin overdose can be treated with this agent (non-rapid reversal)***

Drugs that can precipitate a hemolytic episode in patients with G6PD deficiency

"Hemolysis IS D PAIN": -INH -Sulfonamides -Dapsone -Primaquine -Aspirin -Ibuprofen -Nitrofurantoin Note: Fava beans can also precipitate a hemolytic episode: they increase intracellular oxidative stress and can therefore cause an acute attack in patients with G6PD deficiency who do not have any history of infection and are not taking any medications

FEIBA

(Factor Eight Inhibitor Bypass Activity) -- drug used for the routine prophylaxis to prevent or reduce the frequency of bleeding episodes in patients with hemophilia A or B who have developed inhibitors

Drugs/meds that can cause an absolute or relative folate (vitamin B9) deficiency

-ethanol (suspect folate deficiency in any alcoholic with macrocytic anemia) -oral contraceptives -phenytoin -trimethoprim/sulfonamides -methotrexate

AGENTS FOR REVERSAL

-heparin: protamine sulfate -warfarin: vitamin K (reversal) or FFP/PCC (RAPID reversal) -dabigatran: idarucizumab, PCC, or tranexamic acid -methotrexate: leucovorin (folinic acid)*** -doxorubicin (for prevention of cardiotoxicity): dexrazoxane -HIT: direct thrombin inhibitors (argatroban)

Hodgkin Lymphoma treatment

ABVD protocol: -Adriamycin (doxorubicin): cytotoxic antibiotic -Bleomycin: cytotoxic antibiotic (binds to DNA, causing free radical formation; specific for G2 phase**) -Vinblastine: microtubule inhibitor -Dacarbazine: alkylating agent

kymriah (tisagenlecleucel)

CD19-directed genetically modified autologous T cell immunotherapy indicated for the treatment of patients ≤ 25 old with B-ALL that is refractory or in second(+) relapse; it involves reprogramming a patient's own T cells with a transgene encoding a chimeric antigen receptor (CAR T) to identify and eliminate CD19-expressing malignant and normal cells; approved in 2017 for use in pediatric/young adult relapsed/refractory B-ALL patients; toxicities = cytokine release syndrome (CRS) [may be fatal] (can treat this with tocilizumab), hypogammaglobulinemia, neurological toxicities

atovaquone/proguanil

COMBO antimalarial drug that has synergistic activity against P. falciparum malaria; first drug selectively inhibits the ETC of P. falciparum, while the second drug both inhibits parasite dihydrofolate reductase and potentiates the mitochondrial toxicity of the first drug; used to treat CHLOROQUINE-RESISTANT malaria!!

vorinostat

HDAC inhibitor used to treat MM, cutaneous T-cell lymphomas, and HIV***; it INCREASES histone acetylation and thus enhances gene transcription; it induces cell-cycle arrest, differentiation, and apoptosis of cancer cells, along with increasing transcription of cell-cycle regulators, affecting levels of nuclear TFs, and inducing pro-apoptotic genes; HDAC inhibition also directly blocks function of the chaperone HSP90 and stabilizes the tumor suppressor p53; adverse effects = fatigue, nausea, diarrhea, thrombocytopenia NOTE: addition of this drug to bortezomib treatment overcomes resistance to bortezomib (i.e. for resistant MM tx)

abciximab, eptifibatide

IV anti-platelet drugs that are GpIIb/IIIa receptor blockers (1st drug blocks it directly, second drug blocks fibrinogen from binding to GpIIb/IIIa); unique from other anti-platelets drugs bc they don't block platelet activation --- rather, they block an activated platelet's ability to adhere to other platelets; primarily used for acute coronary syndromes and prior to stenting; main adverse effect = bleeding; can also cause thrombocytopenia (MUST MONITOR PLATELET COUNT!!)

cyclophosphamide

IV or oral pro-drug that requires bioactivation in the liver; it is ultimately converted to a phosphoramide mustard, which is cytotoxic; it is a powerful immunosuppressant (used in vasculitis or glomerulonephritis [oral]); also used for solid tumors, lymphomas, and leukemias [IV form]; adverse effects = myelosuppression, hemorrhagic cystitis (due to toxic metabolite: acrolein)*** (PREVENT hemorrhagic cystitis by co-administering MESNA with this drug), SIADH (hyponatremia may lead to seizures)

dipyridamole

PDE inhibitor that inhibits phosphodiesterase III in platelets (PDE normally breaks down cAMP); thus, you have ↑cAMP levels, which will ↓platelet activation; it also blocks adenosine uptake by cells, which ↑adenosine levels (vasodilation); used with aspirin for stroke prevention (anti- platelet); used in chemical cardiac stress testing (vasodilator); adverse effects (due to vasodilation) = headache, flushing, hypotension

procarbazine

alkylating agent that is part of the MOPP protocol for Hodgkin lymphoma

alteplase, reteplase, and tenecteplase

all of these fibrinolytic drugs are recombinant forms of tPA that also induce the conversion of plasminogen to the active fibrinolytic enzyme plasmin (plasminogen activators!); they increase PT and PTT, but do NOT affect platelet count; like tPA, these are indicated for tx of severe PE, early MI, and early ischemic stroke (within 3 to 4.5 hrs of onset); 1° adverse effect = HEMORRHAGE; CONTRAINDICATED in pt with thrombocytopenia (due to enhanced bleeding risk), or those with recent hx of intracranial bleeding/trauma/surgery NOTE: Compared to the other agents, tenecteplase has a longer half-life and can be administered via IV bolus

doxorubicin, daunorubicin, idarubicin

anthracyclines that have multiple toxic mechanisms that damage DNA and can kill cancer cells; MOA = inhibition of topoisomerase II (breaks with no resealing), intercalation of DNA (insertion b/w base pairs, inhibiting DNA replication/transcription), and generation of free radicals (toxic to cancer cells via DNA oxidative damage); cell-cycle non specific (thus can attack any point of the cell cycle); first drug = WIDELY USED cancer drug; major adverse effect = CARDIOTOXICITY (i.e. systolic HF with necrosis of myocardium 2° to free radical generation) --- can ↓ this drug-induced cardiotoxicity with dexrazoxane**

thalidomide, lenalidomide

anti-MM (anti-multiple myeloma) drugs that act through various mechanisms: (1) direct anti-MM effect on tumor cells including G1 growth arrest and/or apoptosis, even against MM cells resistant to conventional therapy (due to the disruption of the anti-apoptotic effect of Bcl-2 family members, blocking NF-kB signaling, and inhibition of the production of IL-6); (2) inhibition of MM cell adhesion to bone marrow stromal cells due to the reduction in IL-6 release; (3) decreased angiogenesis due to the inhibition of cytokine and GF production/release; (4) enhanced T-cell production of cytokines, such as IL-2 and IFN-gamma, which increase the number/cytotoxicity of NK cells; side effects (mainly first drug) = sedation, constipation, treatment-emergent peripheral sensory neuropathy** NOTE: first drug = prototype; second drug = one of the prototype's derivatives, with less side effects

LMWH (enoxaparin)

anti-coagulant (given via subQ) that acts via ATIII to inhibit Factor Xa ONLY; beneficial because its dose is based on weight (due to reduced binding to plasma proteins/cells), so you don't have to constantly monitor the PTT, and it has a lower incidence of HIT; PTT does not ↑ nearly as much as UFH (not sensitive test for this)

tranexamic acid

anti-fibrinolytic agent that works primarily by forming a reversible complex that displaces plasminogen from fibrin and inhibits the proteolytic activity of plasmin; it can also be used to reverse the anticoagulant effect of direct thrombin inhibitors; by hampering plasmin activity, this drug reduces activation of complement and consumption of C1 esterase inhibitor (C1-INH), thereby decreasing inflammation associated with hereditary angioedema; often used to control local bleeding during dental procedures in patients with hemophilia***

aminocaproic acid

anti-fibrinolytic drug that inhibits plasminogen activation to plasmin, thus there is less breakdown of formed clots; used to treat hemophilia, as it allows whatever factor VIII or IX that is available in the plasma to work more effectively bc plasmin is not breaking down whatever fibrin clots that are formed

methotrexate

anti-folate drug (mimics folate) that inhibits dihydrofolate reductase, blocking the synthesis of THF [tetrahydrofolate] (that is required for DNA, RNA, protein synthesis), which blocks the formation of the nucleotide thymidine (dTMP); used clinically for many malignancies, inc. leukemias and lymphomas; adverse effects = myelosuppression (REVERSIBLE with LEUCOVORIN***), mouth soreness (mucositis), abnormal LFTs, and GI upset; in RARE cases, it can cause drug-induced lung injury: usually a hypersensitivity reaction (if untreated, it can cause pulmonary fibrosis)

quinidine

anti-malarial drug (given via IV) used against resistant Plasmodium species; adverse effects = cinchonism (tinnitus and headaches); used for tx of LIFE-THREATENING cases of malaria

quinolone derivatives (chloroquine, mefloquine, primaquine, quinine & quinidine)

anti-malarial drug class that targets the erythrocytic stage of malaria infection; they function by blocking the detoxification of heme into hemozoin --> heme accumulates and is toxic to plasmodium parasites Note: CANNOT take quinidine or primaquine if you have a G6PD deficiency (these drugs generate ROS that will damage normal RBCs, too, which cannot be repaired bc of the deficiency)

primaquine

anti-malarial drug that can destroy hypnozoites hiding out in the liver (thus, can treat Plasmodium vivax & Plasmodium ovale subtypes), which would otherwise remain dormant in the liver for months-years after infection

chloroquine

anti-malarial drug that is used for the treatment of plasmodial species OTHER than P. falciparum, due to widespread resistance of P. falciparum to this drug (P. falciparum contains a membrane pump that decreases intracellular concentration of this drug); it acts by inhibiting plasmodium heme polymerase, which normally would metabolize free heme to hemozoin (subsequent accumulation of free heme is toxic to Plasmodia); toxicities = retinopathy and pruritus (esp. in dark-skinned individuals)

antifolates (sulfonamides, pyrimethamine, proguanil, dapsone)

anti-malarial drugs that act synergistically to target enzymes involved in folate synthesis, which leads to impairment of parasite DNA synthesis

aspirin

anti-platelet drug that is an irreversible COX inhibitor (COX1 and COX2) that blocks formation of thromboxane A2 (TXA2); it blunts the conversion of arachidonic acid to TXA2 (via inhibition of COX), thus decreasing platelet activity for the lifetime (7-10 days) of the platelet (bc TXA2 = platelet activator, and you are reducing TXA2 levels); it also inhibits the production of prostaglandins (responsible for its pain relief property); most commonly used to treat acute coronary disease (acute MI) and stroke (also used as 2° preventative measure for these conditions); adverse effects = bleeding, gastritis/ulcers, tinnitus, Reye's syndrome (liver failure/encephalopathy in CHILDREN)

ticlopidine, clopidogrel, prasugrel

anti-platelets (thienopyridines) that are irreversible P2Y12 receptor blockers that block the effects of ADP on platelets (thus, decrease platelet activation); used for pt with aspirin allergy or may be added to aspirin regimen for prevention of MI or stroke; major adverse effect = bleeding; RARE, serious adverse effect = TTP*** NOTE: you CANNOT give clopidogrel at the same time as a PPI!!

Babesiosis treatment

atovaquone and azithromycin

lepirudin, argatroban

direct thrombin inhibitors (DTIs) that inhibits thrombin, which will prolong PT, PTT, and thrombin time (bc thrombin activity is common to all of these tests); these two DTIs are only used to treat patients with HIT (heparin induced thrombocytopenia.... where there is a bunch of thrombosis)

vincristine (or vinblastine)

drug that binds ß-tubulin and INHIBITS MICROTUBULES (inhibits microtubule polymerization), preventing spindle formation, and causing mitotic arrest in metaphase; clinically used for many malignancies, inc. lymphomas (part of ABVD protocol for Hodgkin Lymphoma); adverse effects = myelosuppression and NEUROTOXICITY*** (peripheral neuropathy) vincristine for NHL** vinblastine for HL**

autoplex

drug that is indicated for use in patients with Factor VIII inhibitors who are bleeding or are to undergo surgery; IV administration of this preparation is intended to control bleeding episodes in such patients

Yescarta (axicabtagene ciloleucel)

drug that is used for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (refractory DLBCL); given after 2(+) lines of systemic therapy; it is was the first drug type of chimeric antigen receptor T cell (CAR T) therapy; toxicities = cytokine release syndrome (CRS) [may be fatal] (can treat this with tocilizumab), neurological toxicities

hydroxyurea

drug that is used for the treatment of sickle cell anemia and CML (first-line therapies of both); it inhibits ribonucleotide reductase to block conversion of ribonucleotides to deoxyribonucleotides, which stops DNA synthesis/inhibits cell division (inhibits HbS polymerization); it mainly ↑HbF, which is good in sickle cell disease (↓HbS polymerization), along with suppressing the production of leukocytes (↓inflammatory response), which is also helpful; also used for polycythemia vera and essential thrombocytosis

arsenic trioxide (ATO)

drug that is used in treatment of APL during second remission in relapsed patients after ATRA treatment (now considered standard tx for pt with relapse after ATRA/chemo.... highly effective treatment for relapsed APL); it acts by inhibiting thioredoxin reductase to generate ROS, which are quite sensitive to APL cells (that already have a high ROS content)

6-mercaptopurine (6-MP)

drug that mimics purines and inhibits multiple steps in purine salvage (after it is converted to thioinosinic acid), thus inhibiting DNA synthesis; activated (to active metabolite) by HGPRT and inactivated by xanthine oxidase (XO) and TPMT in the liver; clinically used for IMMUNOSUPPRESSION (often used to ween pt off of steroids); adverse effects = myelosuppression, abnormal LFTs, anorexia/nausea/vomiting

treatment options for PNH (paroxysmal nocturnal hemoglobinuria)

eculizumab and/or allogeneic bone marrow transplant eculizumab = humanized mAb that blocks conversion of C5 and formation of the membrane attack complex [MAC] (C5-9), and protects PNH-associated erythrocytes from complement-mediated intravascular hemolysis

erythropoietin (EPO)

endogenous hormone (can be given exogenously) that stimulates erythroid proliferation and differentiation by interacting with erythropoietin receptors on RBC progenitors; it also induces the release of reticulocytes from the bone marrow; tx is MOST EFFECTIVE for anemia pt with chronic renal failure, as EPO levels are low b/c the kidneys cannot produce the GF (less endogenous EPO makes it more likely for the exogenous form to have beneficial effect); this agent consistently improves Hct and Hb level, often eliminating the need for transfusions (esp. in pt undergoing myelosuppressive cancer chemotherapy), and reliably improving QOL; COMMOJ adverse effects = HTN and thrombotic complications (ie. stroke, thromboembolus, CV events) --- MUST keep Hb < 11 to avoid sludgy blood (due to too many RBCs in the blood) and avoid these potential complications NOTE: this therapy is NOT as effective for treating primary bone marrow disorders (i.e. aplastic anemia, leukemia, myeloproliferative disorders) and secondary anemias --- this is because endogenous EPO levels are already high in these patients, so there is less of a likelihood of a response to the exogenous form

plasminogen

endogenous protein (in drug form) that can be used to treat congenital plasminogen deficiency (currently pending FDA approval) and idiopathic pulmonary fibrosis (orphan subtype); it replenishes deficient plasminogen levels in the body to enable a functional fibrinolytic system

tissue plasminogen activator (tPA)

endogenous serine protease that induces the conversion of plasminogen to the active fibrinolytic enzyme plasmin; it increases PT and PTT, but does NOT affect platelet count; indicated for tx of severe PE, early MI, and early ischemic stroke (within 3 to 4.5 hrs of onset); 1° adverse effect = HEMORRHAGE; CONTRAINDICATED in pt with thrombocytopenia (due to enhanced bleeding risk), or those with recent hx of intracranial bleeding/trauma/surgery

fondaparinux

factor Xa inhibitor that avidly binds antithrombin with high specificity, resulting in inactivation of factor Xa; indicated for prophylaxis of DVT that may lead to PE (i.e. patients undergoing hip fracture surgery or knee replacement surgery), treatment of either acute DVT or acute PE when administered with warfarin, and for anticoagulation in patients with HIT

epoetin alfa, darbepoetin alfa

first agent = recombinant human EPO; generally administered 3x per week due to shorter half-life (than second agent) second agent = modified form of EPO that is more heavily glycosylated than first agent, allowing it to have a 2-3X longer half-life; generally administered weekly

fludarabine

fluorinated purine analog that inhibits DNA polymerase, primase, ligase, RNR, terminates DNA chains, and is incorporated in DNA and RNA, and promotes apoptosis; it is used with alkylators to treat CLL***; toxicities = myelosuppression, nausea and vomiting, chills and fever, malaise, anorexia, and weakness

prednisone, dexamethasone

glucocorticoids that act through binding to a specific physiological receptor that translocates to the nucleus and induces anti-proliferative and apoptotic responses in sensitive cells; b/c of their lympholytic effects and their ability to suppress mitosis in lymphocytes, these agents are used as cytotoxic agents in the treatment of acute leukemia --- they produce quick, but short-lived, remission in acute leukemias (AML, ALL)

deferoxamine, deferiprone, deferasirox

if phlebotomy (removal of blood) is contraindicated in a hemochromatosis patient, these iron-chelating agents can be used to remove toxic levels of iron from the body

Treatment of heparin-induced thrombocytopenia (HIT)

immediate discontinuation of heparin along with administration of a non-heparin anticoagulant (e.g. argatroban, bivalirudin, or fondaparinux)

bortezomib

inhibitor of proteasome-mediated protein degradation of IκB, preventing the activation of NF-κB, leading to apoptosis --- central role in treatment of MULTIPLE MYELOMA; toxicities = thrombocytopenia, neutropenia, fatigue, peripheral neuropathy; resistance due to mutations or overexpression of the β5-subunit of the proteasome

treatment of various toxicities relevant to Heme module

iron toxicity: phlebotomy or iron-chelating agent (i.e. deferoxamine) lead toxicity: antidotes include EDTA, penicillamine, dimercaprol, succimer arsenic toxicity: dimercaprol and gastric lavage (stomach pumping: cleaning out the contents of the stomach) mercury toxicity: dimercaprol copper toxicity (i.e. 2° to Wilson's disease): penicillamine NOTE: succimer is used as a chelating agent in children**

rituximab

mAb against CD20 antibody of B-cells, leading to the depletion of B-cells; used in the treatment of CD20+ lymphomas, including follicular B-cell NHL, diffuse large B-cell NHL, and CD20+ CLL (among others); also used to treat ITP (alternate therapy) and rheumatoid arthritis; adverse effects = opportunistic infections (due to depletion of B cells) and hepatitis B reactivation***

alemtuzumab

mAb against the CD52 antigen, which is present on BOTH B-cells and T-cells; it is used to treat B-CLL***

ofatumumab

mAb that binds to CD20 at a DIFFERENT site from that targeted by rituximab; it is used to treat CLL***

(unfractionated) heparin

naturally-occurring polymer that occurs in two forms (unfractionated and low molecular weight [LMWH]); unfractionated form activates anti-thrombin III (ATIII), which will inhibit several factors in the coagulation cascade (esp. intrinsic pathway), including XII, XI, IX, Xa, and Thrombin; given via IV or subQ (acute onset); used for the ACUTE management of DVT/PE, MI, and stroke; can also be used as prophylaxis for DVT in hospitalized patients; it will ↑PTT, thrombin time; dose must be adjusted to reach a "goal" PTT*** adverse effects = mainly bleeding, thrombocytopenia; osteoporosis with chronic use; mildly ↑AST/ALT; HIT (5-10 days after drug therapy) NOTE: protamine can be used as a reversal agent for OD of this Drug (used in OD for this listed drug and/or cardiac surgery)

melphalan

nitrogen mustard alkylating agent that alkylates guanine, causing linkages between strands of DNA, which inhibits DNA/RNA synthesis; these changes cause cytotoxicity in both dividing and non-dividing tumor cells; used to treat MULTIPLE MYELOMA and AL AMYLOIDOSIS***; side effects = nausea/vomiting, oral ulcers, myelosuppression, amnesia

streptokinase

non clot-specific fibrinolytic enzyme (activates plasminogen --> plasmin!!) found within β-hemolytic streptococci; in contrast to the other fibrinolytic agents, this is antigenic and has the potential to cause hypersensitivity reactions including anaphylaxis; most common adverse event associated with its therapy is cerebral hemorrhage***

rivaroxaban, apixaban (note the "Xa" in the names!!!!)

oral direct factor Xa inhibitors (bind to and directly inhibit Factor Xa) used for treatment and prophylaxis for DVT and PE, along with stroke prophylaxis for patients with A-fib; does NOT require monitoring for dosage adjustments (unlike warfarin); adverse effects = ↑risk for spinal/epidural hematoma while taking the drug, discontinuation of this drug by pt with Afib ↑risk for stroke (if it is discontinued for a reason OTHER than pathological bleeding, administration of another anticoagulant should be considered)

dabigatran

orally active prodrug that following metabolism is a DIRECT THROMBIN INHIBITOR; inhibition of thrombin prevents the development of a thrombus -- both free and clot-bound thrombin, and thrombin-induced platelet aggregation are inhibited; therapeutic action of the drug results from the combined activity of both the drug itself and its glucuronides; used prophylactically to ↓risk of stroke and embolism in patients with non-valvular atrial fibrillation; does NOT require routine monitoring for dosage adjustments (unlike warfarin)

pentostatin

potent inhibitor of adenosine deaminase, which leads to build-up of adenosine and deoxyadenosine nucleotides --- this blocks DNA synthesis by inhibiting ribonucleotide reductase; it also increases S-adenosyl-homocyteine, which is also toxic to lymphocytes; used as an alternate agent for tx of HAIRY CELL LEUKEMIA; adverse effects = chronic myelosuppression, fatal pulmonary toxicity when given with fludarabine, GI symptoms, skin rashes, and abnormal LFTs

cryoprecipitate

precipitate that is formed when FFP is thawed and contains factor VIII, vWF, factor XIII, and FIBRINOGEN; older therapy for hemophilia A... now more commonly used as a source of fibrinogen (i.e. to help treat DIC or for massive trauma with blood transfusions) or factor XIII

cladribine (2-CDA)

purine analog (adenosine deaminase inhibitor) that mimics adenosine and is the drug of choice for HAIRY CELL LEUKEMIA; MOA = inhibits DNA polymerase and causes DNA strand breaks: this causes adenosine to accumulate in neoplastic B-cells, which is HIGHLY TOXIC to them; adverse effect = myelosuppression, neurotoxicity, nephrotoxicity

cytarabine

pyrimidine analog that inhibits DNA polymerase (thus, inhibits DNA chain elongation) and is only effective in leukemia and lymphomas (PRIMARY AML TREATMENT!!); adverse effects = myelosuppression, nausea/vomiting, neurotoxicity (high doses), peripheral neuropathy, confusion, cerebellar ataxia, pulmonary edema, dermatitis

filgrastim

recombinant granulocyte colony-stimulating factor (G-CSF) analog used to treat neutropenia in select clinical circumstances

gemtuzumab ozogamicin

semisynthetic derivative of calicheamicin, a cytotoxic antibiotic, linked to a recombinant mAb; humanized mAb is directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML)** NOTE: while it is BANNED, it is currently being reevaluated, as recent studies reported better survival in adults with favorable & intermediate-risk AML that receive this drug along with intensive induction chemotherapy; other studies found less severe, manageable toxicities ---- might be back on the market soon**

α2-antiplasmin

serine protease inhibitor (serpin) responsible for inactivating plasmin (principal inhibitor of plasmin in the circulation); as plasmin degrades blood clots (fibrin mesh), impaired inhibition of plasmin (i.e. due to deficiency of this substance, which is RARE) leads to a bleeding tendency, which can be severe; in cirrhosis, there is decreased production of this substance (because it is synthesized in the liver), leading to decreased inactivation of plasmin and an increase in fibrinolysis (thus, increased risk of bleeding in liver disease)

mefloquine

stronger anti-malarial drug given ORALLY that is used prophylactically for travelers that are traveling to chloroquine-resistant areas; used as treatment or prophylaxis for P. falciparum (including choloroquine-resistant strains) or P. vivax; used to treat CHLOROQUINE-RESISTANT malaria!!

doxycycline, clindamycin

tetracyclines used in combination with other drugs in the treatment of malaria, and as prophylactics for travelers to geographical areas with both chloroquine- and mefloquine-resistant P. falciparum; these drugs act by inhibiting parasite protein synthesis Examples of combo therapies: For chloroquine-resistant P. falciparum: quinine sulfate + doxycycline, quinine sulfate + clindamycin, artesunate + clindamycin

L-asparaginase (L-ASP)

tetramer (pair of dimers that each bind one molecule of asparagine) that deprives lymphoblastic leukemic cells of asparagine by converting it to aspartic acid; unlike normal cells that can synthesize asparagine, these tumor cells require an exogenous source of this AA; adverse effects = severe hypersensitivity rxn that can be fatal (urticaria & full blown anaphylaxis)

romiplostim, eltrombopag

these drugs are alternate agents that can be used to treat thrombocytopenia (LOW platelet count!); 1st drug activates thrombopoietin receptors and used in chronic immune conditions, but NOT cancer; 2nd drug has similar MOA (2nd line agent)

bendamustine

this drug and its active metabolites act as an alkylator and can be used to treat CLL***; it has rapidly reversible myelosuppression mucositis that is tolerable

busulfan

this drug causes severe myelosuppression (severe pancytopenia) --- thus, it is most commonly used to ablate patient's bone marrow (myeloablation) prior to bone marrow transplantation; it can also be used for CML***; toxicities = severe myelosuppression, skin hyper pigmentation, seizures (high dose), and pulmonary toxicity (may progress to pulmonary fibrosis)

oprelvekin (IL-11)

thrombopoietic GF (IL-11) that directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells, which causes increased megakaryocyte maturation and platelet production; used to treat thrombocytopenia (low platelet count)*; used often in chemotherapy

all-trans-retinoic acid (ARTA [vitamin A derivative], tetrinoin)

treatment for acute promyelocytic leukemia (APL, a subtype of AML); acts by binding the altered receptor and causing the blasts to mature (and eventually die)

recombinant factor VIIA

treatment with this results in activation of the extrinsic pathway of blood coagulation; as of 2012, it is not supported by the evidence for treating most cases of major bleeding --- significant risk of arterial thrombosis with its use and thus, other than in those with factor VII deficiency, it should only be given in clinical trials; while initially looking promising in tx intracerebral hemorrhage, failed to show benefit following further study and is no longer recommended

artemisinins (artemether, artesunate)

type of anti-malarial drug used to treat SEVERE malaria infections (i.e. those caused by Plasmodium falciparum); they act by binding iron, breaking down peroxide bridges that lead to the generation of free radicals --- they have the fastest parasite clearance times of any antimalarial and act rapidly, killing blood stages of all Plasmodium species; artemisinin-based combination therapy (ACTs) combine the highly effective short-acting artemisinins with a longer-acting partner to protect against artemisinin resistance and to facilitate dosing convenience IV artesunate = used to treat severe, life-threatening cases of malaria

imatinib, dasatinib, nilotinib

tyrosine kinase inhibitors (TKIs) given orally that are used to treat CML***; first drug = main one: it acts by binding to the ATP site, preventing BCR-ABL (fusion gene due to t(9;22).... Philadelphia chromosome) tyrosine kinase activity; if patient is resistant to the first drug, can use either of the other TKIs; adverse effects = fluid retention (peripheral or periorbital edema) and skin rash Use imatinib for: -CML that is Philadelphia chromosome ⊕ -ALL that is Philadelphia chromosome ⊕ NOTE: first drug (prototype) inhibits the closed (inactive) configuration of BCR-ABL kinase; second drug inhibits both the closed and open (active) configurations of BCR-ABL kinase; third drug has increased potency and specificity for BCR-ABL kinase due to rational design based on the structure of the enzyme & overcomes mutations that cause resistance to the first drug**

desmopressin (dDAVP)

vasopressin (ADH) analog with NO pressor activity (does not increase BP) that is used to treat mild hemophilia A; it can also be used to treat von Willebrand disease, central diabetes insipidus (mimics ADH), and bedwetting (decreases urine volume); it acts by increasing vWF and Factor VIII levels (both released from Weibel-Palade bodies from endothelial cells [where they are stored]); adverse effects = flushing or headache (due to vasodilating properties)