IPCS 2 PK thangz to know

how does first-pass effect bioavailability?

decreases bioavailability

what factors affect volume of distribution?

• Lipid solubility

• Protein binding (plasma)

• Tissue binding

what specific factors decrease volume of distribution?

- low lipid solubility

- high (plasma) protein binding

- low tissue binding

what specific factors increase volume of distribution?

- high lipid solubility

- low (plasma) protein binding

- high tissue binding

what does it mean when a drug has a Vd larger than the total body?

drug extensively leaves blood to go into the tissues

Volume of distribution is most useful for...

estimating loading doses

what are factors that alter Vd and dosing in loading dose?

- Decreased tissue binding

- Decreased plasma protein binding

what is alpha? and what determines alpha?

- alpha = fraction of free/unbound drug

- factors that determine alpha: plasma-protein concentrations and binding affinity

LOW plasma protein concentrations effect on multiple variables:

1. decreased effect on bound drug

2. increased effect on Vd

3. decrease effect on total drug concentration

4. increased effect on alpha

5. no effect on net free drug

how does uremia and phenytoin affect binding affinity?

decreases it

as alpha increases, one should ________ Cp desired by the same proportion

decrease

what factors effect clearance?

1. body size (larger body = increased clearance)

2. protein binding (lower binding = increased clearance)

3. organ function

what is the extraction ratio?

- A measure of how much drug is delivered to a clearing organ vs how much is removed by that organ

-ER of 1.0 means that 100% of the drug delivered to the clearing organ is removed

-ER of 0.5 means that 50% of the drug delivered to the clearing organ is removed

what are the independent variables?

Cl and Vd

increased Cl does what to Ke and t1/2?

increases Ke, decreases t1/2

decreased Cl does what to Ke and t1/2?

decreases Ke, increases t1/2

increased Vd does what to Ke and t1/2?

decreases Ke, increases t1/2

decreased Vd does what to Ke and t1/2?

increased Ke, decreased t1/2

if Cl and Vd change proportionally, then Ke...

does not change

How many half lives does it take to reach steady state?

4-5

how many half-lives for drug to be eliminated?

4-5

what is first order decay represented by?

e^-kt

why is CrCl used?

to assess renal function

what is creatinine?

a by-product of muscle breakdown

how is creatinine eliminated?

Primarily by glomerular filtration + secretion

what is a normal serum creatinine value?

0.6-1.2 mg/dL

what factors affect creatinine production?

age, gender, body mass

what factors affect creatinine clearance?

GFR, renal disease, decreased renal blood flow

what happens to serum creatinine if you increase RA?

it increases

what happens to serum creatinine if you decrease Cl?

it increases

Ra = Re at?

steady-state

how does age effect PK?

- decreased blood flow

- decreased liver mass

- intrinsic metabolic function (phase I: unchanged/decreased and phase II: unchanged)

- age-related changes in different isomers

what are the major reasons a patient will receive dialysis?

Acidosis

Electrolytes

Ingestion/intoxication

Overload

Uremia

when are loading doses adjusted?

if patient is in renal failure + has volume overload, initial dose may need to be increased

what is dialysis?

removes toxins + waste from vasculature

drugs + solutes w/ a MW <500 daltons

what must be in place for a drug to be removed via dialysis?

Molecular weight

- <500 daltons

- urea 60 daltons

- creatinine 113 daltons

- gentamicin 477 daltons

Protein binding

- free drug crosses

- drug-protein complex too large to cross

Flow rates

- dialysate, ultrafiltration, blood flow

FIlter type

How often/long

what is the normal elimination t1/2 in adults + children > 6 months old?

2-3 hrs

what are limitations not accounted for by Hull-Sarubbi nomogram?

- Site of infection

- Severity of infection

- MIC

- pharmacodynamics

- synergy

what is the initial dose and interval for Hartford nomogram?

7 mg/kg