Drugs Affecting Haematopoiesis

Question 1

Drug Classes

Answer 1

GF
Metals
Vitamins

Question 2

GF

Characteristics and Indications

Answer 2

Small glycoprotein molecules

BM depression
After BM transplantation
To harvest progenitor cells
Chronic Renal Failure (–> erythropoietin)

Question 3

RBC GFs

Names and characteristics

Answer 3

Erythropoietin –> Epoietin , Darbepoietin alpha
Recombinant human erythropoietin
Regulate RBC production and maturation
Given IV or SC
Side Effects: flu like symp, hypertension, iron def, increased blood viscosity

Question 4

WBC GFs

Names and characteristics

Answer 4

CSF–> cytokines
stimulate proliferation of progenitor cell and induce differentiation
IV or SC

G-CSF–> filgrastim, pegfilgrastim
stimulate neutrophil progenitor cells
Pegfilgrastim: pegylated–> prolonged duration of action

GM CSF–> molgramostim
Stimulate neutrophil/eosinophil/monocyte/RBC/megakaryocytes
Side Effects: Fever, skin rash, bone pain, GI disorders, hepatosplenomegaly

Question 5

Platelet GFs

Names and characteristics

Answer 5

IL11–> Oprelvekin, Romiplostim

Recombinant IL11–> used post chemo

Recombinant thrombopoietin still under clinical testing

Question 6

Background Iron

Answer 6

Important for syn Hb/Myoglobin/Cytochrome/ other enzymes
Absorbed in Fe2+ (ferrous) form

Vit C: Enhances absorption, reduces ferric–> ferrous
Fructose and AA: increase absorption by forming soluble
complexes
Tetracycline: Inhibits absorption by forming insoluble complex

Mech of Absorption:
Rapid Intake Step: Across Brush border and–> plasma
Rate Limiting, energy dep step: ferrous–> ferric, then bind to transferritin and brought to other side

Storage
Soluble ferritin as ferric; GIT, liver, spleen, BM

Loss
Mainly via stool

Question 7

Side Effects of Iron Preps

Causes of Acute and Chronic Toxicity

Answer 7

Nausea
Vomiting
Abdominal Cramps
Diarrhea, constipation

Acute Toxicity:
GIT bleeding, vomiting, hemorrhage, necrotising gastritis

Chronic Toxicity:
Hemolysis, repeated transfusions

Question 8

Oral Iron Preparations

Answer 8

Ferrous Sulfate
Ferrous Succinate
Ferrous Fumarate

Forms
Tablets, gelatine capsules, enteric coated tablets

FREE IRON IS TOXIC

Question 9

Parenteral Iron Preparations

Answer 9

Iron Dextran
Ferric Gluconate
Iron Sucrose

In case of malabsorption, inflammation, surgical resection
IV

Question 10

Iron Chelators

Answer 10

Desferroxamine
Deferiprone

Th of chronic toxicity
Can be given oral or parenteral

Question 11

Copper

Background and Name

Answer 11

Rare deficiency (only in severe malnutrition)
   due to: inherited transport disorders, long term total parenteral feeding
Can cause microcytic, hypochromic anaemia

Cu-Sulfate
oral, IV

Question 12

Vit B12

Background

Answer 12

Chemical Structure: Hydroxocobalamin
Absorption
active transport from terminal ileum, req. IF (prod in stomach)

Stored in liver

Active form: Methylcobalamin

Action
Req for conversion methyl THF–> THF (acts as cofactor)
Homocysteine–> methionine
blockage: methy-folate trap
Req for conversion methylmalonyl CoA–> succinyl CoA

Deficiency
Increased plasma homocystein conc–> vascular effects–> ROS production–> atherosclerosis

Accumulation of methylmalonyl CoA–> distortion FA synth in neural tissues–> neuropathy

Macrocytic, Hyperchromic Anaemia

Question 13

Vit B12

Name and Characteristics

Answer 13

Hydroxocobalamin (can be used in th of cyanide poisoning as it can take on the cyanide ion

Cyanocobalamin

IV or oral

Question 14

Folic Acid

Background

Answer 14

THF is a methyl donor–> cofactor for DNA synth

Causes of deficiency
   Vit B12 def
   Methotrexate th
   Phenytoin th
   Premie

Question 15

Folic Acid

Name and Characteristics

Answer 15

Folinic Acid
synthetic THF –> converted much more rapidly

Oral

No side effects

Question 16

Other vitamins

Answer 16

Pyridoxine (Vit B6)
Riboflavin (Vit B2)
Both have role in Heme Synth

Vit C def–> iron absorption may be decreased