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Flashcards in Pharmacokinetics/Pharmacodynamics Deck (52)
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0
Q

What factors affect the transfer of drug to various sites within the body?

A

molecular size, degree of ionization, lipid solubility, protein binding, amount of blood flow to the tissue, concentration gradient of the drug across the membrane

1
Q

What is pharmacokinetics

A

concentration of a drug during the processes of absorption, distribution, metabolism, or biotransformation and elimination from the body

what the body does to the drug

2
Q

how does molecular size affect distribution?

A

the smaller the molecule, the more likely it is to cross cell membranes

3
Q

What are SLCs? What do they do?

A

solute carrier transporters – control passive movement of solutes down their electrochemical gradient

4
Q

What are ABCs? What do they do?

A

ATP binding cassette transporters – active pumps requiring energy derived from ATP

5
Q

How does ionization affect lipid solubility?

A

the ionized (charged) form is water soluble

the nonionized (uncharged) form is lipid soluble

6
Q

When the pH = pKa…..

A

charged and uncharged forms exist in equal amounts

7
Q

What is ion trapping?

A

The uncharged part of the drug can cross into the tissue membrane and then the charged portion cannot move back out.

8
Q

The degree of protein binding for a drug is proportional to…

A

its lipid solubility

*the more lipid soluble it is the more it is protein bound

9
Q

How can you overcome protein binding of a drug?

A

Add another agent that competes for the same protein binding sites. This will lead to an increase in fraction of free agent of the 1st drug.

10
Q

What happens to drug concentrations when plasma proteins are low?

A

total drug concentration is lowered but unbound concentrations of the drug are not affected.

11
Q

What is bioavailability?

A

the extent to which a drug reaches its effect site after its introduction into the circulatory system

12
Q

What are some factors that affect bioavailability?

A

age, sex, pathology, pH, blood flow, temperature, etc.

13
Q

Describe the compartments in the 2-compartment model/

A

central compartment - (vessel rich) consists of intravenous fluids, and highly perfused tissues like the brain, heart, kidney, liver, lungs.

peripheral compartment - (vessel poor) composed of muscle, fat, bone

14
Q

How can drugs exit the central compartment?

A

via distribution to the tissues or via metabolism and excretion

15
Q

What is Vd?

A

volume of distribution proportionally relates the amount of drug in the body to the serum/plasma concentration

16
Q

Why is it important to recognize the volume of distribution?

A

it will help you to determine loading doses of drugs to achieve steady-state concentrations

17
Q

How can you calculate Vd?

A

dose of drug / plasma concentration of drug

18
Q

What is the volume of the plasma compartment?

A

4L

19
Q

What is the volume of the interstitial fluid?

A

10L

20
Q

What is the volume of ECF?

A

plasma volume + interstitial fluid = ECF

4L + 10L = 14L

21
Q

What is the intracellular fluid volume?

A

28L

22
Q

What is Total Body Water volume?

A

plasma + IF + ICF = TBW

4L + 10L + 28L = 42L

23
Q

If a drug has a small Vd…. is it lipid soluble?

A

no – likely water soluble and contained to the plasma

24
Q

When might a drug have a large Vd?

A

if it is lipid soluble, unbound to plasma proteins, etc. it will cross into cell membranes and have a large Vd

25
Q

What factor can supercede all other factors when it comes to how a drug behaves in the body?

A

structure/stereochemistry

26
Q

What is a chiral center?

A

a carbon atom with 4 different, asymmetrical bonds

27
Q

As the # of carbons in a molecule increases, so will the # of…

A

possible stereoisomers

28
Q

What is an enantiomer?

A

stereoisomers with non-superimposable mirror images of each other

29
Q

What does the Alpha Phase of the plasma concentration curve represent?

A

initial dispersal of the drug into the tissue compartments from the central compartment

steep slope of the curve if the drug is lipid soluble

30
Q

What does the Beta phase of the plasma concentration curve represent?

A

represents concentration falling exponentially because of elimination of the drug from the body.

usually has a more gradual slope

31
Q

What is goal of drug metabolism?

A

change lipid-soluble agents into more water-soluble forms that can be excreted by the kidneys

32
Q

What is first-order kinetics?

A

drug is cleared at a rate proportional to the amount present in the plasma

33
Q

What is zero-order kinetics?

A

even at a therapeutic level, the drug overwhelms the body’s ability to excrete or metabolize it. Available enzymes for metabolism are saturated. So a constant amount of drug is cleared regardless of the plasma concentration

34
Q

What are phase 1 reactions of metabolism?

A

hydrolysis, oxidation, reduction resulting in increased polarity of the drug molecules

35
Q

What are phase 2 reactions of metabolism?

A

conjugation - drug or metabolite added to endogenous substances like glucuronic acid, sulfonic acid or acetic acid.

36
Q

What enzyme class catalyzes oxidation reactions?

A

cytochrome P450

37
Q

What are microsomal enzymes?

A

reside in the hepatic smooth ER that are responsible for the biotransformation of numerous agents

38
Q

What is enzyme induction?

A

increasing enzyme activity by stimulating the enzymes over a period of time by repeated exposure to a drug or chemical

39
Q

Why is it important to consider enzyme induction when giving drugs?

A

helps you determine dosing intervals because this increased ability to clear drugs will lead to a reduction in the half-lives of many agents

40
Q

What is the elimination 1/2 life?

A

time necessary for the plasma concentration of a drug to drop by 50% after a rapid bolus injection

41
Q

In a practical setting, when is a drug effectively cleared from the plasma?

A

after 4-5 half lives, or about 95% clearance.

42
Q

Clearance of a drug is directly proportional to _____ and inversely related to ______ and _______.

A

the dose of the agent; the agent’s 1/2 life; concentration in the central compartment

43
Q

What are the two main organs for clearance of drugs?

A

liver and kidneys

44
Q

How is clearance mathematically determined?

A

clearance = blood flow x extraction ratio

45
Q

When can the BBB be overcome by a drug?

A

large doses, head injuries and hypoxemia

46
Q

elimination 1/2 time is independent of…..?

A

the dose of the drug delivered

47
Q

What is the 1st Pass Effect?

A

drugs absorbed from the GI system enter portal circulation and can be extensively extracted and metabolized before they reach the effect site

48
Q

What are the 3 most common plasma proteins drugs bind to?

A

albumin (acids)
lipoproteins
Alpha-1 acid glycoproteins (bases)

49
Q

If hepatic extraction for a drug is greater than ____, it’s clearance will depend on hepatic blood flow

A

0.7

50
Q

What is capacity-dependent clearance?

A

when the extraction ratio is low, a decrease in protein binding or an increase in enzyme activity will increase clearance of the drug.

not really affected by hepatic blood flow

51
Q

How can you determine the therapeutic index of a drug?

A

Ratio of LD50 to ED50