Drugs and the Blood (plus additional reading) Flashcards
**Delete any cards from the reading that seem fringe!!
What are 3 presentations (drug characteristics) that may result in changes in protein binding to a drug?
- Highly protein bound (ceftriazone, phenytoin)
- High clearance drugs (particularly those cleared by glomerular filtration)
- Drugs in which dosing is not titrated to effect (or half-life; i.e. antibiotics)
What is most affected by changes in the concentration of the protein-bound fraction of a drug?
The unbound drug concentration
For instance: if the protein-bound drug changes from 99% to 95%, the [unbound] just increased 5 fold
Which has a greater effect: a change from 98% to 94% [protein-bound drug] or from 5% to 1% [protein-bound drug]?
98% to 95%
(a change in concentration for a minimally bound drug hardly affects the conc, dist, clearance or pharmacokin of the unbound portion)
What is most affected by changes in the concentration of the unbound fraction of a drug?
changes in pharmacokinetics
What are 3 ways in which neonatal drug-protein binding varies from adult?
A larger amount of drug remains unbound due to the lower blood concentration of plasma proteins
How will administering a second drug with greater protein affinity affect a previously administered drug?
The second drug will displace the first (which will then alter the balance of bound versus unbound drug)
Why are antibiotics as risk of significant changes in drug pharmacokinetics?
They have multiple half-lives within a single dosing interval
In high clearance drugs, what is most affected by changes in protein binding?
Clearance
Distribution/Vd
What is the most common adverse clinical consequence of G6PD deficiency?
drug-induced hemolysis
-NADPH is not regenerated, thus glutathione is not reduced; reactive O intermediate cannot be removed
What is the function of G6PD?
Protect RBC from oxidative damage
Medications that are contraindicated in G6PD deficiency:
Pegloticase
Quinine
Rasburicase
Sulfamethoxazole
(Did he say we needed to know this?)
What is eryptosis?
suicidal erythrocyte death
How does Ca affect the cell (intracellularly)?
- Activation of Ca-permeable, non-selective cation channels results in increased cytosolic Ca activity
- (Inside the cell) Ca activates Ca-sensitive K channels –> K exits, and the cell becomes hyperpolarized –> Cl exits
- Loss of KCl = loss of water, cell shrinks
How does Ca affect the cell membrane?
Ca stimulates cell membrane scrambling (via inhibition of “scramblase”), which results in breakdown of phospholipid asymmetry and phosphatidylserine exposure at surface
How is Ca involved in eryptosis?
Acts directly on RBC to promote Ca entry via ion channel
What factors can cause a low platelet count?
- Bone marrow doesn’t make enough
- Bone marrow makes enough, but the body destroys them
- Spleen holds on to too many platelets
(or a combination of these factors)
What is the primary manifestation in HIT?
thrombocytopenia
6 risk factors for HIT:
- Female sex
- IV administration of heparin (versus subcut)
- Bovine heparine (versus porcine)
- Post-op patients (worse for ortho srx)
- Heparin exposure for >4 days
- Exposure to unfractioned heparin (versus low-mol-weight)
By what mechanism does HIT occur?
- Heparin/PD4 binds with anti-heparin/PD4-IgG
(drug joins glycoprotein and CDR on antibody) - Immune complex binds to Fc receptor on surface of resting platelet, activating it
- Activated platelet deposits onto subendothelial matrix
In HIT, what may be variable among patients?
severity
timing of onset after heparin
How does non-immune HIT differ from immune HIT?
- Milder
- No antibodies
- Low thrombosis risk
- Onset occurs <5 days after exposure
- Treated via observation (rather than discontinuation of heparin)
What may induce an earlier onset of HIT?
administration of heparin in the past 1-3 months
What may cause a delayed onset of HIT?
formation of heparin-independent antibodies (drug acts as an intermediate in an otherwise weak reaction)
T?F: Heparin is the only drug capable of inducing immune thrombocytopenia.
F (penicillin, quinine, NSAIDs, abciximab, l-dopa, etc)