Block 1 Flashcards by Markus M

What is Pharmacokinetics?

What the body does to the drug

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What is Pharmacodynamics?

What the drug does to the body

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ADME is related to (pharmacodynamics/pharmacokinetics)

Pharmacokinetics

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Why cant receptor sites be measured in regards to drug concentration?

Some are inaccessible such as digoxin’s (found in myocardium)

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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

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What is Emax?

Maximal effect of the body

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What is EC50?

Concentration in plasma that produces 50% of RX’s maximal effect

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What happens to EC50 in regards to tolerance?

Increases

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Potency is the same as (EC50/Emax)

Emax

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What is serum?

Plasma - fibrinogen

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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

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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)

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Zero vs First order elimination

Which one is eliminated at a constant rate per unit time?

Zero order

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Zero vs First order elimination

Which one is eliminated by a constant fraction per unit time?

First order

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Zero vs First order elimination

Which one is more common for drugs to undergo?

First order

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When does zero order elimination typically occur?

Body’s capacity to eliminate Rx has reached its maximum capability

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Elimination rate constant is measured in what?

1/time

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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

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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?

1. Central compartment - vasculature and well-perfused tissues such as lungs and liver 2. 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

1. Injection has been made and drug density is highest in central 2. Rx density is falling rapidly due to distribution. Peripheral has not yet reached the same as central 3. Distribution is equal amongst central and peripheral. Major determinant of Rx disappearance from central becomes elimination process 4. 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