Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Physiology Part 2 > Lec 50 Pharmacokinetics > Flashcards

Lec 50 Pharmacokinetics Flashcards

(76 cards)

Start Studying
1
Q

What is pharmacokinetics vs pharmacodynamics?

A 
pharmacokinetics = what body does to drug
pharmacodynamics = what drug does to bidy
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the four processes of pharmacokinetics? mnemonic?

A

ADME

  • absorption
  • distribution
  • metabolism
  • excretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is definition absorption?

A

movement of drug from site of administration [GI tract] to systemic circulation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is definition distribution?

A

movement of drug from systemic circulation to perfused tissue and between compartments

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is definition metabolism?

A

biotransformation of administered drug

mainly hepatic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is definition excretion

A

removal drugs and their metabolites from body – mainly in urine or bile

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What type of administration of drug bypasses the absorption process?

A

intravenous

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are 4 mechanisms of absorption?

A
  1. diffusion through membranes
  2. diffusion through aqueous intercellular spaces [capillary fenestrations]
  3. through membrane channels
  4. active transport via membrane carriers
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What types of drugs can diffuse through membrane readily? which not?

A

small, non-polar, uncharged molec pass through easily

polar molec not as well

charged molec not at all

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What happens to concentration of drug in systemic circulation for IV vs extravascular administration?

A

IV: will start high and decrease
extravascular: will start low as it is absorbing will increase to peak and then decrease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is bioavailability [F] of a drug? What are its possible values?

A
  • fraction of dose that reaches systemic circulation

- ranges from 0 to 1

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What factors can limit oral bioavailability?

A
  • incomplete absorption from GI tract

- first-past metabolism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Why would you get incomplete absorption from GI tract?

A
  • some of dose undergoes metabolism within intestinal epithelial cells
  • some of dose excreted in feces
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is first pass metabolism?

A
  • drug absorbed through GI enters portal circulation first and passes by liver before reaching the rest of systemic circulation
  • drug may be metabolized within liver so less bioavailability
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Which types of administration have first pass metabolism?

A
  • only oral

- sublingual, intramuscular do not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is CYP3A4?

A
  • enzyme in GI epithelial cell and in liver

- inactivates some percentage of drug that enters

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

How do you calculate bioavailability for time vs plasma concentration graph?

A

bioavailability can be calculated by area under the curve [AUC]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Is AUC for IV drug bigger smaller or same as for oral?

A

bigger AUC = higher bioavailability for IV drug

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Where in the GI tract can drugs be absorbed?

A
  • can take place in all segments of GI tract
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

How does pH affect drug absorption?

A
  • many drugs are weak acids or weak bases

- those ionized in the stomach’s acidic environment will be poorly absorbed there

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is the major site of absorption for most oral drugs?

A

small intestine [particularly duodenum]

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What 3 things determine why most drugs are absorbed in duodenum?

A
  • large surface area
  • longer transit time relative to stomach
  • pH in range that leaves week acids and bases mostly non-polarized so can pass through membranes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

How do extended-release drugs affect their absorption?

A

often designed to be released from tablet at various location along GI

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What 2 factors influence drug distribution?

A
  1. binding to plasma proteins

2. vascularity of tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
What are the 2 most important plasma proteins for drug binding?
- albumin | - a1-acid glycoprotein
26
How does binding to plasma proteins affect drug distribution?
- almost all drugs bind plasma proteins [often 95-99% of total drug in plasma is bound] - only free fraction of drug is available for distribution - drug that binds protein more will have smaller Vd
27
How does vascularity of tissue affect drug distribution?
- drugs distribute faster to highly perfused tissues [brain and heart] - distribution slower to muscle - slowest to adipose tissue and bone
28
What is redistribution?
- drugs distribute between tissues, mediated by return to bloodstream
29
What does VRG stand for?
vessel-rich group = brain and heart
30
What is the volume of distribution?
``` Vd = volume of distribution Vd = A/C A = amount of drug in body C= plasma concentration of drug Vd is the apparent volume = the volume of plasma you would need to hold the amount of drug administered ```
31
What is relationship between amount of drug accumulated in tissue and Vd?
more drug accumulated in tissue = bigger Vd | can often be much bigger than plasma volume
32
What specific type of drugs in particular have large Vd?
lipophilic drugs that accumulate in adipose tissue
33
What are two methods of drug elimination?
- metabolism | - excretion
34
What are the two major organs of elimination?
- liver most important metabolizer, kidney also does some metabolizing - kidney plays role in drug elimination primarily by excreting unchanged drug
35
What is difference elimination and excretion?
- once drug undergoes metabolism it has been eliminated even if metabolites still present in body - excretion is elimination only when the excreted drug is unchanged - excretion of already metabolized drug by urine or bile is NOT elimination
36
What is the rate of elimination?
amount of drug removed from body per unit time
37
What is relationship rate of elimination and plasma drug concentration [C]? What order process?
- first order process [linear] - rate of elimination directly related to plasma drug concentration [C] rate of elim = C* Cl
38
What is pharmacokinetic definition of clearance [Cl]?
- Clearance [Cl] is the constant that relates the rate of elimination to plasma concentration - vol of plasma from which drug eliminated per unit time [plasma volume/time - L/hr]
39
How does clearance [Cl] change as drug administered or eliminated?
- it does not | - clearance is constant, provides single value to characterize the drug's elimination
40
What is equation for Cl?
Cl = Rate of elimination / Concentration [C]
41
What puts max limit on clearance?
- limited by plasma perfusion | - Cl cannot exceed volume that passes through that organ
42
What is max value for clearance of a drug by combined hepatic and renal elimination?
1600 mL/min | 96 L/hr
43
How does plasma kidney perfusion differ from GFR?
- clearance by filtration limited to GFR | - renal secretion and metabolism combined with this allow kidney to have higher clearance
44
What is extraction ratio [E] of organ?
- E is an index of its efficiency in eliminating drug - fraction of plasma cleared of drug during each pass through organ - ranges from 0 [no elimination] to 1 [removes all drug from plasma in single pass]
45
What is equation for E [extraction ratio]?
E = (Cin - Cout) / Cin | Cin and Cout = drug concentration in plasma as it enters and leaves organ respectively
46
What does E=0 mean?
no elimination by the organ
47
What does E = 1 mean?
all drug eliminated from plasma in single pass through the organ
48
What is equation for specific organ clearance?
``` Cl = Q*E Cl = clearance Q = plasma flow E = extraction ratio ```
49
What is renal clearance?
Cl = Q*E = (U*V)/P
50
What is another equation for the extraction ratio of kidney?
E = U/P
51
What is a high extraction drug?
drug with E >= 0.7
52
What is limiting factor of clearance of high-extraction drugs?
= flow limited | - sensitive to perfusion rate of organ since efficiency of organ already very high
53
How is it possible that even some highly protein-bound drugs can have high extraction ratios?
as free drug eliminated within organ, bound drug dissociates and can be eliminated
54
What is relationship high extraction and oral availability?
high extraction = low oral bioavalaibility because 70%+ of drug metabolized during first pass elimination
55
What is a low extraction drug?
- drug with E < = 0.3
56
How does clearance of low extraction drug change with perfusion rate?
- low extraction drug relatively insensitive to perfusion rate - reduced perfusion --> increases extraction ratio by giving elimination more time to act on drug
57
What is limiting factor of clearance of low extraction drugs?
- capacity-limited | - sensitive to enzyme regulation [induction or inhibition]
58
What is equation for total clearance of drug?
Cl tot = Cl hepatic + Cl renal + Cl other
59
What are phase I drug metabolism rxns?
- oxidation/reduction rxns that add or expose active group of drug - produce more polar molec
60
What is consequence of phase 1 rxn?
- metabolite less active than parent drug [often no activity] - polar mole more likely to be excreted by kidney - active group provides substrate for phase II conjugation rxns
61
What type of enzymes catalyzes most phase I rxns?
CYP450s
62
What enzyme in GI works to limit drug absorption?
CYP3A4 [a type of CYP450]
63
What is relationship rifampin and CYP450?
rifampin is a drug induces CYP450 so increases elimination of many other drugs
64
What is an relationship CYP3A4 and grapefruit juice?
grapefruit juice inhibits CYP3A4 in guit | - increases absorption of CYP3A4 substrates
65
Are phase I or phase II rxns catalyzed by CYP450 enzymes?
phase I
66
What are phase II metabolic rxn?
- conjugation endogenous metabolite [glucoronic acid, acetic acid, etc] to active group of drug
67
Are conjugated [phase II products] active or inactive? Whats an example of an active one?
- usually inactive | - exception: morphine glucoronide is active analgeisc
68
Does phase II rxn require phase I rxn already complete?
No - some drugs already have active group present so don't need phase I rxn
69
What drugs mainly excreted in hepatobiliary excretion?
- mainly high molecular weight drugs and metabolites
70
What types of drugs are excreted via glomerular filtration?
- only unbound drugs | - clearance limited by GFR
71
What limits clearance of drugs excreted via glomerulus?
- limited by GFR
72
What is path of drug renal excretion?
- glomerular filtration or secretion [active transport in PT] - then either excreted or reabsorped in PT/DT via passive diffusion or active transport
73
What is fraction excreted unchanged [FEU]?
- fraction of drugs excreted unchanged in urine | - represents net outcome filtration, reabsorption, secretion
74
What is equation for renal clearance of drug [excluding renal metabolism]?
Cl renal = FEU * Cl total
75
What is ion trapping?
- due to pH difference between urine and plasma, ionization of drug in urine can reduce drug reabsorption [and increase excretion] - only uncharged species can be reabsorbed by diffusion
76
What is the henderson hassleback equations?
pH = pKa + log [unprotonated]/[protonated] | = pKa + log [A]/[HA]

Physiology Part 2 (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions