Block 1 Flashcards
What is Pharmacokinetics?
What the body does to the drug
What is Pharmacodynamics?
What the drug does to the body
ADME is related to (pharmacodynamics/pharmacokinetics)
Pharmacokinetics
Why cant receptor sites be measured in regards to drug concentration?
Some are inaccessible such as digoxin’s (found in myocardium)
What is kinetic homogeneity?
Describes the predictable relationship between plasma drug concentration and concentration at receptor site
If drug concentration in plasma increases = concentration in most tissues will increase proportionally
What is Emax?
Maximal effect of the body
What is EC50?
Concentration in plasma that produces 50% of RX’s maximal effect
What happens to EC50 in regards to tolerance?
Increases
Potency is the same as (EC50/Emax)
Emax
What is serum?
Plasma - fibrinogen
When is therapeutic drug monitoring useful?
- Good correlation between pharmacologic response and plasma concentration
- Wide variation in plasma rx concentration from given dose
- Narrow therapeutic index
- Rx’s desired effect cannot be assessed readily by other means
When is therapeutic drug monitoring NOT useful?
- No well defined therapeutic plasma range
- Formation of active metabolites complicates the process unless they are considered
- Wide therapeutic index
- When concentrations do not predict efficacy or toxicity (toxicity occurs at low and high concentrations)
- When high concentrations aren’t particularly toxic (EX: SSRIs)
Zero vs First order elimination
Which one is eliminated at a constant rate per unit time?
Zero order
Zero vs First order elimination
Which one is eliminated by a constant fraction per unit time?
First order
Zero vs First order elimination
Which one is more common for drugs to undergo?
First order
When does zero order elimination typically occur?
Body’s capacity to eliminate Rx has reached its maximum capability
Elimination rate constant is measured in what?
1/time
What is a way to calculate Vd?
Measure plasma concentration immediately after IV admin before any rx has had any chance to undergo elimination
= dose / initial drug concentration
How is Vd affected by Rx that distribute extensively to tissues?
EX: digoxin bound to muscles
Vd = dose / initial drug concentration
Initial drug concentration goes down, therefore Vd goes up
What are some assumptions made for the one compartment model?
- Rx can enter/leave the body aka open compartment model
- Entire body acts as a homogeneous compartment
* Drug concentration in each tissue may not be equal, but is proportional to the concentration in the blood
In regards to ADME, what occurs at the same time in a one compartment model?
Distribution and elimination
What is a drawback to the one compartment model on how it measures concentration?
Predicts plasma conc. as a function of time
It does NOT predict drug conc. in tissues — you need a better model with multiple compartments to make that prediction
If the plasma conc. vs time curve on a one compartment model is not linear, what could have caused this?
Rx may be unevenly distributed to different regions of the body
Dont ever try to “force” the data into a one-compartmental model as it will lead to inaccuracies
A 2 compartment model is utilized when…
- Natural log of plasma conc. vs time is not a straight line
- Plasma conc. vs time profile cannot be characterized by a single exponential function
What are the main compartments in a 2 model compartment?
- Central compartment - vasculature and well-perfused tissues such as lungs and liver
- Peripheral compartment - less well-perfused tissues such as muscle and fa
What are the variables found in the two compartment model (EX: X0, X1…)?
X0 = dose
X1 = amount of rx in central
X2 = amount of rx in peripheral
K12 = rate constant transfer from central to peripheral aka microconstant
K21 = just like K12 but the other way around
K10 = first order eliminatinon rate of rx out of central into urine or feces aka microconstant
3 microconstants exist in this model
Explain the biexponential equation in regards to the two compartment model
Sum of two linear components representing distribution and elimination
Alpha = mostly distribution
Beta = mostly elimination
Drug concentration can be determined by any time by adding them
A or B = C0
alpha/beta = k
Ae^(-alpha * t) + Be^(-beta * t)
Explain the distribution and elimination pattern of the two compartment model
- Injection has been made and drug density is highest in central
- Rx density is falling rapidly due to distribution. Peripheral has not yet reached the same as central
- Distribution is equal amongst central and peripheral. Major determinant of Rx disappearance from central becomes elimination process
- Rx is being “drained” from both compartments. Peripheral to central. Central to out of body. Both are happening at the same rate.
In a two compartment model, drug decline occurs more rapidly in the (distribution/elimination) phase
Distribution
What is the terminal elimination phase?
Period of time when plasma conc. vs time is characterized as a linear process (towards the end)
What are the microconstants in the two compartment model?
K12
K21
K10
What are the macro-constants in the two compartment model?
A, B, alpha, or B
When should you collect samples to calculate half life correctly?
After distribution phase
The extent of absorption is the amount of Rx that reaches where?
Systemic circulation
Determines total AUC
Overall bioavailability can be described as…
F oral = 1 - (f gut + f hepatic)
What kind of drug is lipid soluble to cross cell membrane?
Non-ionized
Protonated form of a weak acid is (ionized/non-ionized)
Non-ionized
Protonated form of a weak base is (ionized/non-ionized)
Ionized
Weak acids are more readily absorbed in the (small intestines/stomach)
stomach
Weak bases are more readily absorbed in the (small intestines/stomach)
small intestines
What are the uptake transporters?
OATP (organic anion transporting polypeptide)
What are the efflux transporters?
P-gp (P-glycoprotein)
Which transport (uptake or efflux) molecule produces metabolites?
None, only CYP3A4 does
OATP take parent drug from small intestines to portal blood
P-gp brings parent compound back to small intestine
What do the techniques of residuals help with in regards to absorption?
Separate the 2 processes of absorption and elimination
Used to evaluate rates of absorption between 2 different drugs or on 2 different formulations of the same drug
A higher Ka indicates a (faster/slower) absorption rate
faster
Steeper line, and most likely a higher Cmax
What is lag time in regards to absorption?
Absorption of Rx does not start immediately after ingestion
Physiologic factors are at play like stomach-emptying time and intestinal motility
DO NOT get lag time confused w/ onset time
Onset time represents latency which means the time required for Rx to reach minimum effective concentration
