Pharmacology: Drugs and the Blood

Question 1

What drug characteristics increase the consequences of plasma protein displacement?

Answer 1

Drugs that are highly protein bound, have high clearance rates, and where dosing is not titrated to effect suffer more severe consequences from plasma protein displacement.

Question 2

Why is displacement of highly plasma protein bound drugs extremely important?

Answer 2

Because very small changes in plasma binding in highly bound drugs translate into large changes in active unbound drug concentrations

Question 3

Is plasma protein binding consistent for the same drug?

Answer 3

No, there may be some variability in plasma binding of the same drug between patients.

Question 4

Do newborns or adults usually have more or less drug bound to protein?

Answer 4

Usually adults have a higher proportion of protein bound drug than newborns.

Question 5

What is G6PD deficiency?

Answer 5

G6PD deficiency has been associated with drug induced hemolysis.

Question 6

Adverse reactions to drugs are dependent on what drug factor?

Answer 6

Dose

Question 7

Why are some drugs contraindicated in G6-PD deficiency?

Answer 7

Pegloticase, Quinine, Rasburicase, Sulfamethoxazole.

Question 8

How do some drugs cause Eryptosis?

Answer 8

Some drugs increase the RBC permeability to Ca which stimulates the loss of K and cell membrane scrambling that can lead to eryptosis.

Question 9

Why is the scramblase enzyme important?

Answer 9

Scramblase maintains the proper makeup of the cell membrane.

Question 10

What general factors lead to thrombocytopenia?

Answer 10

Bone marrow does not produce enough.
The body destroys platelets.
The spleen holds too many platelets.
Or any combination of these factors.

Question 11

What is heparin induced thrombocytopenia?

Answer 11

PF4 binds to heparin causing it to become an antigen for antibodies. Takeup by platelets causes platelet activation, aggregation, and decreased numbers of platelets available for normal clot formation.

Question 12

What are fractionated heparins?

Answer 12

Fractionated heparins are fragments of heparin that are smaller but have similar effect.

Question 13

Why is the drug (heparin) needed for HIT?

Answer 13

Because with all drug induced antibody bindings the complex of drug and antigen is required for antibody binding

Question 14

What is the most common cause of peripheral blood cytopenias in the industrial world?

Answer 14

Myelosuppression is easily the most common cause of cytopenias in the developed world.

Question 15

How can drugs cause myelosuppression (generally speaking)?

Answer 15

myelosuppression can occur by decreased bone marrow production or shortened peripheral blood survival.

Question 16

What is idiosyncratic myelosuppression?

Answer 16

Idiosyncratic myelosuppression is achieved by shortening peripheral blood survival.

Question 17

What are some non-cytotoxic mechanisms of myelosuppression?

Answer 17

Induction of defects in hematopoietic cells, damage to stromal microenvironment,
Inhibition or destruction of growth factors.
humoral or cellular immunosuppression.

Question 18

How is drug induced myelosuppression managed?

Answer 18

Rapid empiric antimicrobial therapy must be used if infection is suspected. Also EPO, G-CSF, and GM-CSF can be used to try and stimulate blood cell development.

Question 19

What is drug induced agranulocytosis?

Answer 19

Many drugs are associated with rare instances of agranulocytosis which is a deficiency of granulocyte production.

Question 20

What is unique about the timeline of drug induced agranulocytosis?

Answer 20

It is highly variable between drugs and some drugs do not exhibit agranulocytosis until they have been given for a substantial period of time.

Question 21

What are antiplatelet drugs?

Answer 21

(1) Thromboxane inhibitors
(2) PAR1 antagonists
(3) ADP receptor antagonists
(4) Alpha 2 B3 inhibitors (prevent aggregation)

Question 22

What are fibrinolytic drugs?

Answer 22

Drugs that cause clots to break up.

Question 23

What are anticoagulation drugs?

Answer 23

Drugs that prevent the formation and propagation of clots. (warfarin, heparins, dabigatran)

Question 24

What is the major concern associated with non-vitamin K targeted anticoagulants targeted at thrombin ?

Answer 24

There is no way currently to stop severe bleeding should it occur in patients taking drugs like dabigatran.

Question 25

How can erythropoietin be used therapeutically?

Answer 25

EPO can be used therapeutically to stimulate the production of RBCs

Question 26

What is one of the major concerns associated with EPO treatment?

Answer 26

EPO is also known to increase the susceptibility to malignant transformation in the bone marrow.

Question 27

What are some of the adverse effects of folic acid deficiency?

Answer 27

Folic acid deficiency can lead to megaloblastic anemia and glossitis.

Question 28

What other deficiency can lead to Folic acid deficiency?

Answer 28

Cobalamin deficiency can lead to folic acid deficiency, neurological disease, subacute combined degeneration

Question 29

What does iron deficiency lead to?

Answer 29

Iron deficiency leads to anemia.

Question 30

What is the major concern with giving iron supplements?

Answer 30

Iron supplements can be very toxic. Kids have been known to take too many because they look like candy. Chelating agents may be given to counter act the iron toxicity.

Question 31

What are some of the effects therapeutic G-CSF?

Answer 31

(1) G-CSF stimulates Neutrophil production/mobilization

(2) Activates Endothelial cells
(3) stimulates monocyte production/activation
(4) suppresses T cells
(5) mobilizes type 2 dendritic cells.

Question 32

What are some the the therapeutic effects of GM-CSF?

Answer 32

GM-CSF activates and mobilizes Monocytes, neutrophils, Eosinophils, Dendritic cells and NKT cells.

Question 33

What are the risk factors for HIT?

Answer 33

Heparin exposure greater than 4 days
unfractionated heparin
post-operative patients (orthopedic)
bovine heparin
IV administration
female sex