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Flashcards in Week 4 Pharmacokinetics Deck (71):
1

what are the fundamental questions regarding medication? 3

how to deliver, what concentration, how long should the medication be taken for

2

what are the benefits (2) and drawbacks (1) of topical medication admin

Topical: + immediately effective, long lasting, - most most drug action sites are internal

3

define pharmacokinetics

what the body does to the drug

4

what are the four factors affecitng pharmacokinetics

ADME. Absorption, Distribution, Metabolism, excretion

5

what are seven common routes of drug admin?

1. oral 2. IV 3. Topical 4. rectal 5. injection 6. inhaled 7. sublingual

6

what is the first-pass effect

drugs that are absorbed through the GI tract must first pass through liver before going to systemic circulation. the liver detoxifies some of the drug and concentration decreases

7

what are four ways in which oral drugs are lost?

1. stool 2. detoxed by liver 3. binds plasma proteins/ends up in adipose (free drug=active drug) 4. excreted

8

what does MEC stand for? what are the two types associated with drugs?

minimum effective concentration. MEC for desired response. MEC for adverse response.

9

what is the therapeutic window of a drug?

between MEC for desired response and MEC for adverse response

10

most drugs are absorbed actively/passively due to their _____/____ nature. this type of absorption is/ is not saturable and therefore displays ___ order kinetics

passively hydrophobic/uncharged (easily pass through membrane) not saturable first order kinetics

11

the pKa for a weak acid is...

12

the pKa for a weak base is

>7

13

most drugs are what type of acid or base?

weak acid or base

14

what form of WA/WB are readily absorbed

uncharged form

15

when decreasing pH what form does WA/WB take

WA: HA (uncharged) WB: HB+ (charged)

16

when increasing pH what form does WA/WB take

WA: A- (charged) WB: B (uncharged)

17

Aspirin is a weak acid drug, will increasing intestine pH increase aspirin absorption?

decrease absorption HA+H20==>A- + H3O+ (more of the deportonated charged form)

18

what is bioavailability?

the amount of an oral drug that actually reaches systemic circulation and can be used by the body

19

if given a graph of [plasma drug] vs time of an injected drug and orall drug, how can you calculate the bioavailability

BA: Area under curve oral/AUC injected X100

20

what factors limit the bioavailability of a drug? 5

some drugs are degraded in acid of stomach, some drugs are not efficiently absorbed in GI tract, micororganisms in GIT metabolize drugs, first pass effect

21

what factors impact the distribution of drugs in the body? 4

blood flow, capillary permabeability, binding of drugs to plasma proteins/tissues, hyrdrophobic/hydrophilic drugs

22

how does blood flow impact drug distribution?

some organs receive more blood flow (brain, liver, kidney>muscle, skin, fat) and therefore more exposure to drugs in circulation

23

how does capillary permeability impact drug distribution?

some capillaries are less permeable. brain capilllaries less permeable than liver capillaries

24

what is a drug resevoir?

drugs bind plasma proteins and in tissues, these drugs are not active. when the free drug concentration decreases, these drugs will be released.

25

what are the two "compartments" of the body/

central compartment (circulation), peripheral compartment (body tissues)

26

what is the alpha phase?

an initial rapid decline in [plasma drug] that is a result of body tissues binding/sequestering drug. eventually an equilibrium is obtained

27

what is the beta phase?

decrease in drug concentration due to removal from the body (metabolism/excretion)

28

what is the volume of distribution?

how much drug needs to be put in the body to get a certain [plasma drug].

29

what is the eqn for Vd

Vd=amount of drug in the body (amount given, mg)/drug concentration in plasma (mg/L)

30

a 70 kg man has how many liters of plasma? liters of blood?

3 L of plasma, 5.5 L of blood

31

drug metabolism GENERALLY activates/inactivates a drug

generally inactivates

32

the enzymatic modifications of drugs typically make the drug more...

hydrophilic/polar so they can be excreted

33

what is a prodrug?

a drug that is inactive but activated by metabolism

34

where does drug metabolism mainly occur?

liver

35

what are the two phases associated with drug metabolism?

Phase I, phase II

36

what is a phase I reaction? main enzyme?

oxidation, hydrolysis, hydroxylation, dealklylation, deamination. CYTOCHROME P450s (odxidation, reduction, hydrolysis)

37

what is a phase II reaction?

addition of a large substituent group (glucuronyl, sulfate, acetyl) that makes the compound more POLAR

38

Cytochrome P450s: location, role, typical structural feature of substrates

most important enzyme for drug metabolism, over 57 P450s in human genome. located in membrane of ER (mainly in liver), high lipid solubility is a common structural feature

39

general rxn that CYP (cyt P450 catalyze)

NADPH+ H+ +R +O2==>NADP+ + H2O + RO

40

microsomal (ER) enzymes can be activated by... (3 examples)

repeated exposure to some drugs: ethanol, phenobarbital, carcinogenic cmpds

41

microsomal enzymes can be inhibited by....(3)

decrease activity of CYP. Imdazole containing drugs, some antibiotics, grape fruit juice

42

how many Cytochrome P450s account for 95% of drug metabolism? which is the biggest contributor

6 Cyt P450 enzymes. CYP3A4

43

what is the M-M eqn?

v=(Vmax[C])/(Km+[C]), [C] is drug concentration

44

when [C]>>>>Km, what does the M-M eqn look like? what order kinetics?

v=(Vmax[C]^0); zero order reaction. V is independent of [drug]; saturated (drugs that need a transport protein)

45

when [C]

v=(Vmax[C])/(Km); first order reaction. V is dependent on drug concentration; non-saturated (passive diffusion of drugs)

46

most drug elimination resembles which order kinetics?

first order, the rate (-dC/dt) of disappearance is dependent on the concentration of the drug

47

what is the integrated rate law for 0 order reactions?

[C(subt)]=-kt+ [C(sub0)]

48

what is the integrated rate law for a 1 order reaction?

ln[C(subt)]=ln[C(sub0)]-kt

49

the rate of disappearance for a drug having zero order kinetics is...

-dC/dt=k; elimination has become saturated

50

the rate of disappearance for a drug having first order kinetics is....

-dC/dt=K[C]; elimination is not saturated

51

what is half-life of eliminaiton?

the amount of time required for the concentration of drug in the blood to decrease by 1/2

52

what is t(1/2) for a first order reaction

=.693/k

53

what is t(1/2) for a zero order reaction?

=[C(sub)]/(k*2)

54

what is clearance?

CL; the volume of plasma cleared of the drug per unit time (L/hr)

55

does clearance for most drugs depend on concentration of the drug?

YES! most drugs depict a first order elimination. -dC/dt=kC

56

what equation related CL and Vd?

k=CL/Vd

57

what equation relates half life (first order), Vd, and CL?

t(1/2)=(.693(Vd))/CL

58

a pt took 10 mg IV injection of a drug and the plasma drug concentration was 1 mg/mL. 10 hrs later the drug concentration was .25 mg/L. what is CL

1.4 L/hr

59

what is the (Css) steady state concentration of a drug?

seen during drug accumulation (repeated dose of a drug, contstant rate IV), this is when the rate of infusion=rate of elimination (first order reaction, the concentration of the drug gets high enough where its eliminanation matches its accumulation)

60

If rate of infusion (IV infusion) increases then what happens to Css

Css increases (directly proportional, double rate=double Css)

61

if the clearance of a drug increases (is doubled) what happens to Css?

Css halves (inversely proportional)

62

when do we see CL decrease?

liver or kidney disease

63

what is clearance?

how fast the drug is eliminated from the body

64

what determines the time to reach the steady state? exception?

changed only by factors that change t(1/2). only factors that alter elimination (increase metabolism of a drug or increase clearance will both decrease the amount of time to reach Css). Exception is a loading does that will attain Css faster due to a higher initial dose

65

a pt takes a drug with regular repeated oral doses. which may result in shorterr time required to reach Css? 1. shorten the dose interval by 50% 2. increase drug dose by 2x 3. take a drug that induces the P450 enzyme 4.take a drug that inhibits P450

3. inducing P450 will increase the CL and the Css will be reached faster

66

changing the rate of infusion of a drug changes the final Css/time to Css, but does not alter the final Css/ time to Css

changes the final Css does not change time to Css

67

relate Css value and frequency of dose (oral) and interval of dose

Css=frequency/interval of dose as frequency increases, Css increases as interval increases, Css decreases

68

relate Css value and dose of a drug

Css is directly proportional to dose. increase dose, increase Css (the time to Css does not change!!)

69

if a drug is not metbaolized by the liver very well, what is a possible side effect?

the drug accumulates in the body

70

rate of elimination=

CL x [C]

71

Label: 

onset of effect, topical admin, oral admin, duration of action, peak effect, intensity, MEC for advers, MEC for desired, therapeutic window

 

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