Hematology

Question 1

Oral Iron Therapy

Answer 1

Subject to the regulatory mechanism provided by the intestinal uptake system
No need to monitor iron storage levels

Ferrous iron (Fe2+)  is used, because it is best absorbed
 Ferrous sulfate, Ferrous gluconate

Iron therapy should be continued for 3-6 months after correction of iron loss

Question 2

Adverse Effects: Oral Iron Therapy

Answer 2

Adverse effects: epigastric discomfort, abdominal cramps, constipation, diarrhea

Dose-related-can be remedied by backing off the dose

Patient may have fewer adverse effects with one iron salt than another

Question 3

Parenteral Iron Therapy: Iron Dextran

Answer 3

Adverse effects: headache, light-headedness, fever, nausea, vomiting

rarely anaphylaxis may occur due to the dextran component-a small test dose should always be given

Caution with patients with a strong history of allergy or who have previously received iron dextran

Since the intestinal regulatory system is bypassed, more iron can be delivered than can be safely stored in intestinal cells and macrophages

Question 4

Parenteral Iron Therapy: Iron Sucrose Complex,

Sodium Ferric Gluconate Complex

Answer 4

Iron Sucrose Complex, Sodium ferric gluconate complex

May only be given IV

Less likely to induce a hypersensitivity reaction

Question 5

Iron Toxicity

Answer 5

As few as 10 tablets of commonly available oral iron salts can be lethal in young children

Starts with necrotizing gastroenteritis, followed by lethargy, shock, dyspnea-there is then improvement, but this may be followed by severe metabolic acidosis, coma, death

Urgent treatment is necessary-whole bowel irrigation and treatment with deferoxamine

Chronic iron toxicity (e.g., hemochromatosis) can be treated with deferasirox

Question 6

Deforoxamine

Answer 6

Treatment for iron toxicity

Urgent treatment is necessary-whole bowel irrigation and treatment with deferoxamine

Question 7

Deferasirox

Answer 7

Chronic iron toxicity (e.g., hemochromatosis) can be treated with deferasirox

Question 8

Vitamin B₁₂ Deficiency

Answer 8

Megaloblastic, macrocytic anemia

Leukopenia and/or thrombopenia

Hypercellular bone marrow

Neurological deficits: paresthesia, weakness, spasticity, ataxia, dementia

Usually due to malabsorption rather than a nutritional deficiency, especially in the elderly

Question 9

Vitamin B₁₂

Answer 9

B12-porphyin-like ring w/ a central cobalt atom + a nucleotide-organic groups may covalently bind to cobalt, forming different cobalamins

Deoxyadenosyl-cobalamin and methylcobalamin are the active forms of the vitamin in humans

Cyanocobalamin and hydroxycobalamin are found in food sources and drugs-converted to active form

Source of B12 is from microbial synthesis-not made by plants or animals-get it from microbially derived b12 found in meat, egg, dairy-sometimes called extrinsic factor

Question 10

B₁₂ Absorption

Answer 10

Absorbed only after complexing with intrinsic factor, which is secreted by the cell of the gastric mucosa

B12-intrisic factor complex is absorbed in the distal ileum via a receptor-mediated transport system

Once absorbed, B12 is transported to the various cells of the body bound to transcobalamin II

Excess B12 goes to the liver for storage

Question 11

Erythropoietin

Answer 11

Endogenous erythropoetin is produced by the kidneys

When there is tissue hypoxia, erythropoietin synthesis is increased in order correct the anemia

There is an inverse relationship between hematocrit/hemoglobin levels and erythropoietin levels, except in renal failure

Stimulates erythroid proliferation and differentiation by interacting with erythropoietin receptors on red cell progenitors; can also induce induce release of reticulocytes from the bone marrow

EPO receptors signal through the JAK/STAT kinase pathway

Question 12

Darbepoetin alpha

Answer 12

Glycosylated EPO

Mainly used in patients with anemia of chronic renal failure

May also be useful for treatment of anemia due to primary bone marrow disorders and secondary anemias, if the patient has disproportionally low serum EPO levels for their degree of anemia

Question 13

Romiplostim

Answer 13

Peptide bound to a Fc portion of a human antibody that activates thrombopoetin receptors on megakaryocytes to stimulate platelet production

For use in pts with chronic immune thrombocytopenia, but NOT for use in pts with thrombocytopenia due to myelodysplastic syndrome or chemotherapy

Question 14

Eltombopag

Answer 14

Small molecule thrombopoeitin receptor agonist

Reserved for pts with severe ITP that fail to respond to other tx

Question 15

IL-11/Oprelvekin (recombinant IL-11)

Answer 15

Stimulates the growth of multiple lymphoid and myeloid cells for patients with thrombocytopenia due to chemotherapy

Acts synergistically with other growth factors to stimulate the growth of primitive megakaryocytic precursors
Increases the number of peripheral platelets and neutrophils

Side effects: fatigue, headaches, dizziness

Question 16

Indirect Thrombin Inhibitors

Answer 16

Examples: Heparin, LMWH, Fondaparinux

inhibitors-bind to antithrombin and increases the rate at which antithrombin inhibits coagulation factors
Antihrombin can inhibit factors Xa, IIa, IX, VII and V

conformational change occurs that exposes the active site on antithrombin for more rapid interaction with proteases- particularly factor Xa

Act as cofactor for the antithrombin-protease reaction without being consumed; released intact from the complex for renewed binding to more antithrombin

Question 17

Heparin

Answer 17

All of these compounds have the pentasaccaride-this is what binds to antithrombin and induces the conformational change;

heparin, because of its large size efficiently accelerates the rate of Xa and IIa inhibition

must monitor activated partial thromboplastin time to ensure therapeutic level has been reached
Usually given via continuous IV infusion

Can be reversed with Protamine Sulfate

Can cause Heparin-induced thrombocytopemia; development of IgG antibodies against heparin bound to platelet factor 4, leading to thrombosis and thrombocytopenia

Question 18

LMWH, fondaparinux:

Answer 18

More predictable pharmacokinetics vs. heparin when given subcutaneously

No monitoring needed

Question 19

Heparin-induced thrombocytopenia

Answer 19

Immune complex formation between heparin and platelet factor 4

Complex is seen as a foreign substance

Antibodies are formed against the complex=destruction of platelets

Platelet disruption leads to formation of new clots and may result in a deep vein thrombosis, pulmonary embolism, heart attack or stroke

An alternative anticoagulant must be used, e.g., a direct thrombin inhibitor

Question 20

Lepuridin, Desirudin

Answer 20

Recominant derivatives of hirudin

Directly inhibits thrombin by competitively binding to thrombin’s catalytic site and the extended substrate recognition site

May be used in patients with HIT

Caution in those with renal insufficiency

Question 21

Treatment of Rocky Mountain Spotted Fever

Answer 21

-low threshold for treatment if symptoms after dog-tick or wood-tick bite (abdominal pain, rash on ankles)

Doxycycline for adults and children (risk of brown teeth vs high risk of death)

Chloramphenicol for pregnant women

other blood-borne bacteria:

• Orientia Tsutsugasmushi: doxycycline or chloramphenicol
• Coxiella Burnetii: doxycycline
• Ehrlichia chaffeensis: doxycycline

Bartonella sp.: azithromycin or erythromycin

Question 22

Tetracycline

Answer 22

inhibits protein synthesis in bacteria

mRNA attaches to the 30s subunit or rRNA. The P site of 50s rRNA contains nascent polypeptide chain. Tetracycline binds the A site, therefore charged tRNA cannot enter to add to the polypeptide

Question 23

Chloramphenicol

Answer 23

Binds 50s rRNA subunit at peptidyltransferase site and inhibits the transpeptidation rxn.

Same binding site as clindamycin and macrolides so these agents interfere with binding of chloramphenicol.

Toxicity: anemia, leukopenia, thrombocytopenia; also an idiosyncratic response by aplastic anemia.

Question 24

Chloroquine

Answer 24

Antimalarial

1-2 month half life

Accumulates in the food vacuole of parasite and inhibition of the formation of hemozoin from the heme released by digesting hemoglobin.

Resistance: decreased accumulation in the food vacuole.

Does not eradicate hepatic forms so must be used with primaquine to eradicate P. vivax and P. ovale

mefloquine, lumefantrine, quinine have similar MOA’s

Question 25

Primaquine

Answer 25

Antimalarial

converted to electrophiles that generate ROS that interferes with e- transport in parasite

Question 26

Atovaquone

Answer 26

Antimalarial

interferes with e- transport in the mitochondria of malarial protozoa

Question 27

Artesunate

Answer 27

release of actice oxygen species from endoperoxide bond kills the malarial parasite

Question 28

Artemether-lumefantrine

Answer 28

ACT partner drug combo that assures sustained antimalarial action by overcoming Artemether’s short half-life and is actice against multi-drug resistant P. falciparum

Question 29

Pyrimethamine-sulfadoxine

Answer 29

synergistically inhibits plasmodial DHF reductase/thymidylate synthase and PABA utilization.

Resistance has limited its use

Question 30

Proquanil

Answer 30

Inhibits DHF reductase/ thymidylate synthase; actice against both primary liver and asexual red cell stages.

Question 31

Clindamycin

Answer 31

Binds 50s subunit of bacterial ribosomes to suppress protein synthesis by inhibiting translocation step like the macrolides.

Babesia have eukaryotic cytoplasmic ribosome so cilndamycin is ineffective; however, their mitochondria and plastid ribosomes are prokaryotic.

Question 32

Azithromycin

Answer 32

same MOA as macrolides but differs from erythromycin b/c of its lactone ring, which reduces drug interactions due to cytochrome P-450

Question 33

Quinine and Quinidine

Answer 33

same MOA as chloroquine

differ from each other at the carbon bearing the secondary alcohol

Question 34

Acute Lymphoblastic Leukemia

Answer 34

Hoezler/Linker based protocol

Phase 1 (1-4 weeks): vincristine, prednisone, daunorubicin, L-asparaginase

Phase II (5-8 weeks): cyclophospamide, cytarabine and 6-mercaptopurine

prednisone induces apoptosis in lymphocytes to produce quick but short lived remission

Question 35

L-Asparaginase

Answer 35

deprives lymphoblastic leukemic cells of Asparagine by converting it to Asparatate

Tumor cells can’t synthesize Asparagine

Asparaginase is a tetramer made of a pair of dimers. Each dimer binds one molecule of asparagine.

Treatment for ALL phase I

Question 36

Acute Myelogenous Leukemia

Answer 36

For most types, AML is treatment is built around cytarabine (Ara-C):

7+3: Cytarabine for 7 days and daunorubicin or idarubicin or mitoxanthrone days 1-3.

HDAC: High-Dose Ara-C (cytarabine)
Gemtuzumab ozogamicin – accelerated FDA-approval agent that was recently removed from the market due to prolonged myelosupression and hepatocellular damage in 40% of patients.

For acute promyelocytic leukemia (APL) with an aberrant retinoic acid receptor-alpha, treatment is by all-trans-retinoic acid (ATRA) plus daunorubicin or idarubicin. Arsenic trioxide for a second remission in relapsed patients after ATRA treatment.

Question 37

Cytarabine

Answer 37

The trans 2’ OH group of cytarabine inhibits DNA chain elongation after the activated cytarabine-triphosphate is incorporated into DNA (steric hindrance of base rotation). Resistance is by cytidine deaminase and dCMP deaminase as well as deficiency of deoxycytidine kinase (no phosphorylation to active form).

Question 38

Idarubicin and Mitoxantrone

Answer 38

Idarubicin acts like doxorubicin

Like doxorubicin and idarubicin, mitoxanthrone intercalates with DNA and binds to topoisomerase II to inhibit chromosome separation in mitosis, but it cannot be reduced in the presence to iron to form semiquinones (no 4th ring). Hence, no oxygen radicals are formed yielding lower cardiac toxicity.

Question 39

Chronic lymphocytic leukemia (CLL)

Answer 39

Withhold treatment in asymptomatic, early-stage patients (watchful waiting).

CLL is treated with fludarabine, cyclophosphamide, rituximab (sometimes in combination), alemtuzumab, ofatumumab, chlorambucil, bendamustine.

Chlorambucil is metabolized to active phenyl acetic acid mustard. Given orally, it generally is well tolerated

Bendamustine and its active metabolites act as an alkylator with rapidly reversible myelosuppression and mucositis that are tolerable.

Question 40

Fludarabine/ Cladribine

Answer 40

A fluorinated purine analog is fludarabine. It inhibits DNA polymerase, is incorporated in DNA and RNA, and promotes apoptosis. It is used to treat chronic lymphocytic leukemia. Cladribine is the chlorinated version of fludarabine. Both agents are resistant to deamination, which is the major resistance for cytarabine.

Question 41

CML

Answer 41

Chemotherapy with Gleevec (imatinib mesylate)- first-choice therapy, often in combination with hydroxyurea. Imatinib resistance has led to the use of dasatinib or nilotinib.

Allogeneic stem cell transplantation (allo-SCT)
Interferon-alpha and busulfan treatments- no longer used

CML is characterized by a 9;22 translocation known as the Ph chromosome. The product of this fusion gene is Bcr-Abl tyrosine kinase, which is thought to be leukemogenic

Gleevec is an inhibitor of Bcr-Abl kinase
Inhibition of Bcr-Abl kinase is an effective therapy for CML

Question 42

Hydroxyurea

Answer 42

Hydroxyurea inhibits ribonucleoside diphosphate reductase to block the conversion of ribonucleotides to deoxyribonucleotides, a crucial step in DNA synthesis

Question 43

Imatinib/ Dasatinib/ Nilotinib

Answer 43

Imatinib inhibits the closed or inactive configuration of BCR-ABL kinase. It binds the ATP site to inhibit the tyrosine kinase actiivity. Used to treat Chronic Myelogenous Leukemia.

Dasatinib inhibits both the closed and open (active) configurations of BCR-ABL kinase.

Nilotinib has increased potency and specificity for BCR-ABL kinase due to rational design based on the structure of the enzyme and overcomes mutations that cause imatinib resistance.

Question 44

Hairy Cell Leukemia (HCL)

Answer 44

First choice drugs: cladribine and pentostatin if disease progresses and symptoms appear.

Rarely, patients who don’t respond to chemotherapy or have discomfort because of a very enlarged spleen (caused by leukemia cells growing in the spleen) may have the organ removed by surgery (splenectomy).

Rituximab also shows promise.

Question 45

Pentostatin

Answer 45

Pentostatin is a potent inhibitor of adenosine deaminase, which leads to build-up of adenosine and deoxyadenosine nucleotides. This blocks DNA synthesis by inhibiting ribonucleotide reductase that produces the deoxynucleotides.

Question 46

Hodgkin’s Disease or Lymphoma

Answer 46

Treatment by MOPP: Mechlorethamine, vincristine (Oncovin), procarbazine, prednisone. (Classic)
ABDV: Doxorubicin (Adriamycin), bleomycin, vinblastine, dacarbazine. (Newer)

Question 47

Non-Hodgkin’s Lymphoma (NHL)

Answer 47

Treatment depends on the grade of NHL: low, low/intermediate, high/intermediate or high-grade.

For advanced high/intermediate-grade NHL: R-CHOP: Rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone

R-EPOCH (dose adjusted): Rituximab, etoposide, doxorubicin, vincristine, prednisone, cyclophosphamide, filgrastim using neutrophil count as a marker.

Question 48

Multiple Myeloma

Answer 48

bortezomib, dexamethasone and thalidomide or lenalidomide.
bortezomib, pegylated liposomal doxorubicin, dexamethasone
High-dose melphalan or cyclophosphamide and prednisone, followed by bone marrow or peripheral blood stem cell rescue (transplantation).

Melphalan is a direct alkylator similar to mechorethamine

Question 49

Thalidomide

Answer 49

More than a teratogen

Anti cancer drug:

. Direct anti-MM effect on tumor cells including G1 growth arrest and/or apoptosis, even against MM cells resistant to conventional therapy. This is due to the disruption of the anti-apoptotic effect of Bcl-2 family members, blocking NF-B signaling, and inhibition of the production of IL-6. B. Inhibition of MM cell adhesion to bone marrow stromal cells due partially to the reduction in IL-6 release. C. Decreased angiogenesis due to the inhibition of cytokine and growth factor production and release. D. Enhanced T-cell production of cytokines, such as IL-2 and IFN-, that increase the number and cytotoxic functionality of natural killer (NK) cells.

Question 50

Bortezomib

Answer 50

inhibitor of proteasome-mediated protein degradation of IκB, preventing the activation of NF-κB, leading to apoptosis. Central role in treatment of multiple myeloma.

Question 51

Naked Monoclonal Antibodies (Mab)

Answer 51

Rituximab is used to treat B cell non-Hodgkin lymphoma. It is a monoclonal antibody against the CD20 antigen, found on B cells.
Ofatumumab is a Mab that binds to CD20 at different site from that targeted by rituximab.

Alemtuzumab is an antibody against the CD52 antigen, which is present on both B cells and T cells. It is used to treat B cell chronic lymphocytic leukemia (B-CLL).

Naked monoclonal antibodies kill tumor cells by:
ADCC: antibody-dependent cellular cytotoxicity
CDC: complement-dependent cytotoxicity

Question 52

Rituximab

Answer 52

RITUXIMAB bound to a protein on the CD20 antigen found on the surface of normal and malignant B lymphocytes. The Fab domain of Rituximab binds to the CD20 antigen on B lymphocytes, and the Fc domain recruits immune effector functions to mediate B-cell lysis in vitro.

Question 53

Conjugated monoclonal antibodies

Answer 53

Conjugated monoclonal antibodies are joined to drugs, toxins, or radioactive atoms. They are used as delivery vehicles to take those substances directly to the cancer cells. The MAb acts as a homing device, circulating in the body until it finds a cancer cell with a matching antigen. It delivers the toxic substance to where it is needed most, minimizing damage to normal cells in other parts of the body.

Gemtuzumab ozogamicin consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic, linked to a recombinant monoclonal antibody. HP67.6 represents the humanized monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML).

Question 54

Bivalirudin

Answer 54

Directly inhibits thrombin
Alternative to heparin in patients undergoing coronary angioplasty

Question 55

Agatroban

Answer 55

Binds reversibly to the catalytic site of thrombin
Metabolized by P450-caution in those with hepatic insufficiency

Question 56

Warfarin

Answer 56

MOA: inhibits Vitamin K reductase. No reduced vitamin K for use in carboxylation reactions.

Clinical use: to prevent progression/reoccurrance of deep vein thrombosis or pulmonary embolism; also used in acute MI and chronic atrial fibirllation. Given orally

Toxicity: birth defects; bleeding

Drug Interactions, C/I
Avoid drugs that inhibit CYP2C9 (e.g., fluxoetine, cimetidine, clopidogrel)
No vitamin K: will reduce anticoagulant effects by increasing activation of clotting factors

Reversal of Action: excess bleeding can be stopped by vitamin K or recombinant Factor VIIa
Due to warfarin’s long t_1/2, a single dose may not be sufficient to reverse its effect

Question 57

oral anticoagulants

Answer 57

Dabigatrin etexilate
MOA: reversible blockade of thrombin active site_._No monitoring needed

Rivaroxaban
MOA: oral Xa inhibitor
No monitoring needed

Question 58

Fibrinolytics

Answer 58

Lyse thrombi by catalyzing the formation of plasmin from plasminogen

Clinical uses:
Acute MI
Acute ischemic stroke

Tissue plasminogen activator (t-PA): preferentially activates plasminogen bound to fibrin, which confines fibrinolysis to the thrombus BUT at therapeutic concentrations, the level of t-PA is high, creating a systemic lytic state

Recombinant forms of t-PA: Alteplase, Reteplase, Tenecteplase

Toxicity: hemmorrage, treat OD with aminocaproic acid, an inhibitor of fibrinolysis

Question 59

Antiplatelet Drugs

Answer 59

Aspirin: COX-1 inhibitor

Dipyramidole, Cilostazol: blocks reuptake of adenosine, leading to increased cAMP

Abciximab: Monoclonal antibody directed against IIb/IIIa receptor complex.

Eptifibatide: Analog of the extreme carboxy terminal sequence of the delta chain of fibrinogen

Question 60

Platelet ADP Receptor Inhibitors

Answer 60

Ticlopidine: blocks ADP receptors, can cause neutropenia

Clopidogrel: a more potent inhibitor of ADP receptors

Prasugrel: also inhibits ADP receptors; prodrug

Ticagerlor: another ADP receptor antagonist

Inhibit platelet aggregation by irreversibly blocking ADP receptors. Inhibit fribrinogen binding by preventing glycopretoin IIb/IIIa from binding to fibrinogen. (Remember Ib binds vWF)

Used in acutre coronary syndrome, decreasing incidence or recurrence of thrombotic stroke

Question 61

Tranexamic acid, Aminocaproic acid

Answer 61

Fibronolysis inhibitors used to treat bleeding disorders

MOA: block the interaction of plasmin with fibrin

May also be used to treat bleeding from fibrinolytic therapy

toxicity: intravascular thrombosis, hypotension, abdominal discomfort, diarrhea

Question 62

Vitamin K

Answer 62

used to treat bleeding disorders

Confers biological activity upon prothrombin and factors VII, IX, and X

Two natural forms exist: K1 and K2
K1-found in food
K2-found in human tissues, and is made by intestinal bacteria
K1 is available clinically in oral and parental forms
Rapid infusion of K1 can produce dyspnea, chest and back pain, death, so go slow when infusing iv
Deficiency occurs most frequently in patients in intensive care units

Question 63

Plasma fractions used to treat bleeding disorders: Desmopressin, Autoplex, Cryprecipitate

Answer 63

Plasma-derived, heat- or detergent-treated factor concentrates or recombinant factor concentrates are standard therapy for bleeding associated with hemophilia

Desmopressin acetate
Increases factor VIII activity in those with mild hemophilia A or von Willebrand disease

Autoplex, FEIBA (factor eight inhibitor bypassing activity)
Factor IX concentrates that contain activated clotting factors
Used for treating patients with inhibitors or antibodies to factor VIII or IX

Cryoprecipitate
Plasma protein fraction from whole blood
Used to treat deficiencies or qualitative abnormalities of fibrinogen or in patients with factor VIII deficiency and von Willebrand disease

Question 64

Dimercaprol

Answer 64

Chelator

Antidote against arsenic poisoning

May also be used for acute lead intoxication in conjunction with EDTA

Unstable in aqueous solution, so given as a 10% solution in peanut oil

Must be given i.m. (painful!)

Readily absorbed, metabolized and excreted by the kidney within 4-8h after administration

High incidence of adverse effects:
Hypertension, tachycardia, nausea, vomiting, lacrimation, salivation, fever (especially in children), pain @ injection site

Question 65

Succimer

Answer 65

Water-soluable analog of dimercaprol

Protects against the lethal effects of acute arsenic poisoning

Can also be used to increase excretion of lead

Oral formulation only in U.S.
May not be advisable for use in acute arsenic poisoning when severe gastroenteritis and splanic edema may limit its absorption

Adverse side effects are uncommon, but may include:
GI disturbances
Rashes

Question 66

Edetate Calcium Disodium (EDTA)

Answer 66

Primarily used for the chelation of lead

Should only be administered as calcium disodium salt

Life-threatening depletion of calcium can occur if not given as the calcium disodium salt

Chelates extracellular metal ions due to poor penetration of cell membranes

Poor oral absorption due to highly polar nature
administered i.v.
Oral administration may actually increase lead absorption in the gut

EDTA is rapidly excreted by glomerular filtration; also induces rapid excretion of lead in the urine
Excretion of drug and metals may be delayed in patients with renal insufficiency
C/I in anuric patients

Question 67

Unithiol

Answer 67

Another water soluble analog of dimercaprol

Increases excretion of arsenic and lead

May be given orally or i.v.

Has no FDA-approved indications, but may be advantageous over i.m. dimercaprol or oral succimer in treating severe acute arsenic poisoning

Can also serve as an alterative to oral succimer in the treatment of lead intoxication

Has a low incidence of side effects

When given i.v., must be given slowly over 15-20 min, as it may cause vasodialation and hypotension

Question 68

Penicillamine

Answer 68

Derivative of penicillin

Readily absorbed, resistant to metabolic degradation

Primarily used to prevent copper accumulation, but can increase excretion of lead

One-third of patients show adverse effects
Hypersensitivity-exercise caution in patients with a history of penicillin allergy
Nephrotoxicity
Pancytopenia with prolonged use

Question 69

Deferoxamine

Answer 69

Binds iron avidly

Poorly absorbed when given orally
Can increase iron absorption when given via this route

Does not compete for biologically chelated iron

Chelator of choice for iron poisoning
Usually given i.v. or i.m.
If given i.v., it must be done slowly, as rapid administration can cause hypotension

Adverse idiosyncratic responses have been observed, but generally side effects are minimal

Question 70

Acute inorganic lead poisoning

Answer 70

Initial therapy-parenteral-limited to <5 days
I.V. EDTA (~30-50 mg/kg/d) by continuous infusion OR
I.M. dimercaprol, followed 4h later by concurrent administration of dimercaprol and EDTA

After 5 days-oral therapy
succimer

*The end point for chelation therapy is the resolution of symptoms or the return of blood lead concentration to the pre-morbid range

Question 71

RHo(D) immune globulin

Answer 71

Prevents Rh hemolytic disease of the newborn

Consists of plasma-derived IgG that contains a high titer of antibodies against the Rh (D) antigen found on the surface of RBCs

When given 24-72h after the birth of a Rh-(+) infant, Rho (D) immune globulin will suppress the Rh (-)mother’s antibody response to foreign Rho (D)-positive cells

Infant’s RBCs will be cleared from circulation before the mother can generate memory B cells that could produce anti-Rho (D) antibodies if they were to be activated during a subsequent pregnancy with an Rho (D)-positive fetus

Mother must be Rho (D)-negative, or not previously immunized to the Rho (D) factor

Treatment is advised for Rh-negative mothers that have had miscarriage, ectopic pregnancy or abortion; basically, any time when the blood type of the fetus is unknown

Must not be given to the infant

Infrequent adverse reactions

Question 72

Vemurafenib

Answer 72

Small molecule inhibitor of forms of the B-Raf kinase with the V600E mutation

Used to treat metastatic melanoma