CPR1 - Pharmacology {1.10,1.14,2.11}

What are the advantages of PO iron?

Effective for most patients, extremely low risk of adverse events, initial costs very low

What are the advantages of IV iron?

Effective for most patients, more rapid correction, ability to administer large doses, adherence is assured, no GI side effects

What are disadvantages of PO iron?

GI side effects, Adherence may be low, may inadequate, administration for several months

What are the disadvantages of IV iron?

Requires monitored IV infusion, rare cases of allergic or infusion reactions, requires equipment and personnel to treat allergic or infusion reactions

Why should IV iron be avoided with active infections?

Many infectious agents thrive on iron

What are the stages of iron toxicity?

Early GI symptoms, latent GI symptoms, shock and persistent metabolic acidosis, delayed hepatotoxicity, remote bowel obstruction

What drugs are treatments for iron toxicity?

Deferoxamine, deferasirox, deferiprone

What is the mechanism of action for Deferoxamine, deferasirox, deferiprone?

Complexes with trivalent ions, primarily in the vascular space, to form ferrioxamine, which is eliminated in the urine by the kidneys

How is a folate (B9) deficiency treated?

Daily PO folic acid

How is B12 deficient anemia treated?

Hydroxocobalamin or cyanocobalamin

What are the indications for treatment with EPO (Epoetin alfa/darbepoetin alfa)?

Anemia related to CKD, Chemotherapy recipients, anti-retroviral recipients, myelodysplastic syndrome

What is the mechanism of action fro epoetin alfa/darbepoetin alfa?

Induces erythropoiesis by stimulating division and differentiation of erythroid progenitor cells, induces the release of reticulocytes

What are the indications for avatrombopag (TPO)?

Chronic immune thrombocytopenia, chronic liver disease associated thrombocytopenia

What is the mechanism of action of avatrombopag (TPO)?

small molecule TPO receptor agonist that stimulates proliferation and differentiation of megakaryocytes

What are the adverse reactions of avatrombopag (TPO)?

Bruising, petechia, gingival hemorrhage

What are the indications of sargramostim (GM-CSF)?

neutropenia, acute myeloid leukemia, bone marrow transplantation, chemotherapy induced myelosuppression, hematopoietic radiation treatment syndrome

What is the indications fro Luspatercept?

Beta-thalassemia

What is the mechanism of action for luspatercept?

Receptor is fused to the Fc portion of an IgG1, inhibits TGF-β reducing Smad2/3 signaling

What are the indications for Eltrombopag (TPO)?

Aplastic anemia, chronic immune thrombocytopenia, chronic Hep C

What is the mechanism of action for Eltrombopag (TPO)?

Non-peptide agonist of TPO receptor

What are the adverse reactions of Eltrombopag (TPO)?

Nasopharyngitis, upper respiratory infection

What are the indications for Romiplostim (TPO)?

Acute radiation syndrome, chronic immune thrombocytopenia

What is the mechanism of action for Romiplostim (TPO)?

Peptide analog of TPO receptor

What are the adverse reactions of Romiplostim (TPO)?

Bruises, skin rash

What is the mechanism of action for Filgrastim (G-CSF)?

G-CSFs stimulate the production, maturation and activation of neutrophils

What are the indications for Sargramostim (GM-CSF)?

Neuroblastoma, acute myeloid leukemia, bone marrow transplantation, hematopoietic radiation treatment syndrome

What is the mechanism of action for Sargramostim (GM-CSF)?

Stimulates proliferation, differentiation, and functional activity of neutrophils, eosinophils, monocytes and macrophages

What are the indications for hydroxyurea?

Sickle cell anemia

What is the mechanism of action for hydroxyurea?

Increased hemoglobin F (HgF) levels, RBC water content, and alters RBC adhesion to endothelium

What are the adverse reactions and toxicity for luspatercept?

Hypertension, peripheral edema, arthralgia, myalgia, abdominal pain, nausea, diarrhea, elevated LFTs, kidney impairment, do not use 3 months before pregnancy or during pregnancy

What drugs are prophylaxis for malaria?

Chloroquine, primaquine, atovaquone-proguanil, doxycycline, mefloquine, tafenoquine

What drugs should you give a patient who has malaria that is resistant to chloroquine?

Atovaquone-proguanil or artemether-lumefantrine

What is the mechanism of action for chloroquine?

Blood schizonticide, concentrates in vacuoles preventing proper heme breakdown

What are the pharmacokinetics of chloroquine?

Oral - rapid and comple absorption, large Vd, 3-5 day initial half-life, long terminal half-life 1-2 months

What are the adverse effects of chloroquine?

Pruritus somewhat common in africans, large list of rare events, Avoid in patients with a history of anxiety, depression or psychosis

What is the mechanism of action of atovaquone?

Disrupts mitochondiral ETC, active against both tissues and blood schizonts, can discontinue at one week post exposure

What is the mechanism of action of proguanil?

DHFR inhibitor, most effective against blood schizonts, also works on liver schizonts

How is atovaquone-proguanil administered?

Oral, poor absorption, administer with food or milk-based drink daily

How is atovaquone-proguanil eliminated?

Atovaquone - feces, proguanil - urine

What are the adverse effects of atovaquone-proguanil?

Nausea, abdominal pain, vomiting, increased ALT and AST, headaches and dizziness, puritis

What is the mechanism of action of mefloquine?

Unknown, destruction of asexual blood forms of the malarial pathogens

How is mefloquine administered?

Only oral, 20 day half-life, dose weekly

How is mefloquine metabolized?

Extensively hepatic primarily by CYP3A4

How is mefloquine excreted?

Primarily bile and feces

What are the adverse effects of mefloquine?

GI effects, behavioral disturbances (Black box), dizziness, sedation, seizure, vivid dreaming

What is the mechanism of action of primaquine and tafenoquine?

Unknown, eradicationf of dormant liver forms of vivax and ovale

How is primaquine and tafenoquine administered?

Oral, good absorption, 3-8 hour half-life

What are the adverse effects of primaquine and tafenoquine?

One metabolite implicated in hemolytic anemia, arrhythmia, dizziness, prolonged Q-T interval, pruritus, skin rash

What is the drug of choice for pregnant patients with malaria?

Chloroquine

What causes of malaria are best treated with primaquine and tafenoquine?

P. vivax and P. ovale

What must happen before treatment of malaria with primaquine and tafenoquine?

Screening for G6PD deficiency

What is the mechanism of action for tetracyclines (doxycycline)?

Competitively blocking the binding of tRNA to the A site of the 30S subunit, preventing addition of new amino acids to the growing peptide chain

What are the adverse effects of tetracyclines?

GI inflammation/ulceration, discoloration of the teeth and hypoplasia of the enamel, phototoxicity

What are some contraindications for tetracyclines?

Pregnant women after four months of gestation, should not be taken with milk

What is the mechanism of action for artemether-lumefantrine?

Converted into free radicals in the parasite food vacuole and a calcium ATPase inhibitor, blood schizonticide

What is the mechanism of action for lumefantrine?

Unsure, possibly inhibits the formation of β-hematin

What should not be given to patients with asymptomatic Babesia microti?

Antimicrobial therapy

What is the appropriate drug for a mild babesia microti infection?

Atovaquone plus azithromycin

What is the appropriate drug for a severe babesia microti infection?

Clindamycin plus quinine

What is the appropriate drug for a babesia divergens infection?

Complete RBC transfusion, Clindamycin + Quinine