doping and cardiovascular drugs of abuse

Question 1

what is erythropoietin

Answer 1

anti inflammatory hormone normally produced and secreted in the body, upregulated when needed

glycoprotein produced by kidneys

stimulates red blood cell production from bone marrow at specific times e.g. if loss of blood cells in wound

maintains oxygen supply to tissues indirectly via red blood cells

suppresses apoptosis

Question 2

erythropoiesis

Answer 2

stimulation of bone marrow to produce red blood cells

Question 3

red blood cell lifespan

Answer 3

90 days

Question 4

overstimulation of erythrocyte pathway

Answer 4

can cause overproduction of immature, inefficient reticulocytes which dont have as much o2 carrying capacity as erythrocytes

cause anemia, some leukemias

Question 5

erythropoietin mechanism

Answer 5

hypoxic conditions (e.g. high altitude)

kidneys enhance erythropoietin gene expression

inc erythropoietin hormone secretion into blood

goes to bone marrow rbc production sites

inc rbc production

negative feedback, inc rbc causes it to turn off once normoxic environment sustained

(EPO binds to EPO receptors, triggers JAKSTAT and MAPK pathways - anti apoptosis)

Question 6

additional systemic functions of erythropoietin - 5

Answer 6

angiogenic protection (blood vessels)

cardiac protection

neuroprotection

wound healing stimulation

renal protection

Question 7

therapeutic uses of artificial erythropoietin - 4

Answer 7

renal disease

chemotherapy when bone marrow destroyed

myelodysplasia - blood cancers

HIV

Question 8

erythropoietin is referred to as __. as is available in 4 types:

Answer 8

EPO:

EPO alpha
EPO beta
EPO zeta
darbepoietin alfa

Question 9

erythropoietin administration

Answer 9

subcutaneous injection daily

Question 10

erythropoietin half life

Answer 10

depends on preparation, between 2-140 hrs

Question 11

erythropoietin side effects

Answer 11

inc arterial blood pressure as volume inc

inflammation can cause thromboembolism, cvd events

tumour growth as anti apoptotic

Question 12

what is blood doping

Answer 12

used by athletes to improve athletic performance to inc oxygen carrying capacity

Question 13

3 methods of blood doping

Answer 13

inc RBC number by transfusion

use of blood products

stimulating body to produce more RBCs e.g. training in hypoxic chambers

Question 14

side effects of blood doping

Answer 14

enhanced infection and illness

Question 15

aims of blood doping - 3

Answer 15

inc blood volume and haemoglobin conc - by inc haemoglobin mass

inc heart rate and stroke volume (more blood pushed out when heart contracts) - by maximising cardiac output

inc oxygen affinity of blood and mitochondrial efficiency - by inc release of oxygen into tissues

all of these inc aerobic capacity

Question 16

VO2max testing

Answer 16

amount of oxygen respired when exercising until exercised until exertion - at full capacity

aim is to inc VO2max

Question 17

blood doping also commonly interacts with

Answer 17

steroid use

Question 18

when was blood doping banned

Answer 18

1990s

world anti-doping agency now use western blots to detect rEPO

Question 19

HIF (hypoxia inducible factor) stabiliser

Answer 19

form of blood doping

HIF released when normal normoxia achieved

causes HIF prolyl hydroxylase release, turns off system and reduces EPO secretion

HIF stabilisers block HIF prolyl hydroxylase release, body continues hypoxia, does not turn off

Question 20

myo-inositol trispyrophosphate

Answer 20

form of blood doping

inc oxygen release from haemoglobin

inc oxygen supply to skeletal muscle

Question 21

perflurocarbons

Answer 21

form of blood doping

inc oxygen solubility in blood, dissolves in blood

inc oxygen carrying capacity without needing RBCs

Question 22

cobalt chloride

Answer 22

form of blood doping

normally used in treatment of anemia

mimicks hypoxic environment, upregulation of EPO by kidneys

Question 23

cobalt chloride side effects

Answer 23

heavy metal poisoning of blood

can be fatal