Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

443 - Pharmacology & Toxicology > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

What is pharmacokinetics?

A

What the body does to the drug

A mathematical description of movement of a drug over time through the body
* time to onset of clinical effect
* magnitude of the drug’s effect
* duration of action

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

What are the 4 main processes involved in drug pharmacokinetics?

A

Absorption
Distribution
Metabolism
Elimination

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

There is a relationship between the concentration of the drug in an easily measurable “compartment” (eg., blood) and its …

A

effect

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

What is typically assessed in terms of drug concentrations?

A

Plasma drug concentrations

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

Which organs are associated which each part of ADME?

A

Absorption - Small intestine
Distribution - Cardiovascular system
Metabolism - Liver
Elimination - Kidney

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

What is the primary site of absorption of orally administered drugs?

A

Small intestine

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

What is the primary site of drug metabolism?

A

Liver

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

What is the primary site of drug elimination?

A

Kidney

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

How are concentration-time curves generated?

A

A drug is administered then serial blood samples are taken to measure the drug concentration in the body

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

This curve would indicate which type of administration? Why?

A

IV admin, no absorption phase since the drug enters the plasma directly

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

What aspects of the concentration-time curve should be at each blank?

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

What does the drop on a drug’s concentration curve indicate?

A

It represents the elimination phase, that elimination of the drug exceeds absorption.

Remember: All of the ADME processes occur simultaneously so they are all still occuring during this stage, there is just more elimination.

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

What is Cmax?

A

The highest concentration achieved by the drug in the plasma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Cmax is determined by…

A

the amount and bioavailability of the drug administered, and the relative rates of absorption, distribution to the tissues, and metabolism/elimination.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is Tmax?

A

Tmax is the time at which the drug reaches its highest (measured) concentration in plasma

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

Cmax and Tmax are influenced by…

A

chosen sample collection times.

True Cmax and Tmax are not known, since samples are not taken continuously. The more samples that are taken the better the concentration-time profile will be defined.

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

What does the area under the curve (AUC) represent?

A

AUC (Area Under the Time-Concentration Curve) is a measure of the animal’s total exposure to the drug

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

What is the half-life of a drug?

A

The time it takes for the plasma concentration of the drug to decrease by half.

Half-life = T1/2

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

The half-life of a drug varies with…

A

where on the curve it is calculated.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Where on the curve should half life be calculated?

A

Typically, the half life reported for drugs and used to develop dosing schedules is the terminal elimination half-life, which is calculated using the slope at the right side of the curve AFTER absorption and distribution are mostly complete.

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

Why is half-life important?

A

Half-life is important for determining accumulation of drug when multiple doses are given.

The relationship between the half-life and the frequency of dosing will determine the steady state plasma drug concentration (and thus, total exposure of the animal to the drug).

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

How much is the duration of action of a drug extended when the dose is doubled?

A

Doubling the dose extends the duration of action by an extra half life.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What factors determine duration of drug effect?

A
  • The half-life of elimination
  • The dose
  • The effective concentration
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What does the dosing interval have to be to “fully” clear the drug between each dose?

A

The drug will be fully cleared between each dose if the interval is greater than 5 half-lives

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What determines the dose of a drug?

A

Generally determined by minimum effective concentration and toxic concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

What determines the dose interval?

A
  • Clearance and half-life
  • The minimum therapeutic concentration
  • The maximum safe concentration

Dose interval = times per day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

What is Css?

A

The average steady state drug concentration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

What is steady state?

A

Steady state occurs after multiple drug doses when the average drug concentration no longer changes. This occurs when the amount of drug going into the body is equivalent to the amount of drug leaving the body over the dosing interval.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

In steady state, the rate of elimination = ?

A

dosing rate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

When does steady state occur?

A

After 5 half-lives, as long as the dosing interval is less than 5 half lives.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

If steady state is achieved and more frequent & lower doses are given (but same mg/kg/day), how would that change Css?

A

Css would not change!

However, the magnitude of the fluctuations would be reduced.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

How would Css change if the dose of a drug is increased but the dosing interval is the same?

A

Css would increase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

What factors affect Css?

A
  • Bioavailability
  • Clearance
  • Dose
  • Dosage interval
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Drugs with short half-lives require ____ to allow accumulation to the desired Css.

A

more frequent dosing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Drugs with a ____ require more frequent dosing to reduce the magnitude of the fluctuations in concentration between the start and finish of the dosing interval.

A

low therapeutic index/narrow therapeutic range

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

On a BID or SID dosing schedule, will prednisone accumulate and reach steady state?

T1/2 =1-2 hours

A

No, since both BID and SID dosing are more than 5 half-lives, the drug will not accumulate and steady state will not be reached.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

What is clearance?

A

Clearance is the (conceptual) volume of plasma that would need to be cleared of drug to account for its removal per unit time.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

How can clearance be determined?

A

From average concentrations at steady state

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

What is the formula to calculate clearance after a single dose administration?

A

Cl = dose/AUC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

How can you shorten the time until a clinical effect is seen if the drug has a long half-life (days to weeks)?

A

Give a loading dose, which is a single larger dose given at the start of therapy

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

What is a loading dose?

A

A single larger dose given at the start of therapy.

Loading dose = Vd x desired drug concentration

42
Q

How much of a drug is cleared from the blood by 5 half lives?

A

> 95%

43
Q

How much of a drug is cleared from the blood by 10 half lives?

A

> 99%

44
Q

How long are withdrawal times?

A

Approx 10 half-lives

45
Q

What is drug absorption?

A

Drug absorption refers to movement of the drug from its site of administration to the blood

46
Q

Absorption is not considered to factor into the pharmacokinetics when a drug is administered ___.

A

intravenously

47
Q

All ADME processes require the drug to pass through ____.

A

cell membranes

For absorption, the drug must pass through mucosa or skin (if given orally or topically) into the interstitial space, and then through capillary walls into the blood.
During distribution the drug must then pass from the blood through capillary walls to the target tissue. It may reside in the extracellular fluid or may pass intracellularly into the cytosol or specific organelles within the cell.

48
Q

What type of drugs are more readily absorbed, why?

A

Lipophilic drugs are more readily absorbed since drugs must pass through a hydrophobic membrane to be absorbed.

49
Q

How are lipid-soluble molecules transported across cell membranes?

A

Lipid-soluble molecules can diffuse across membranes down a concentration gradient.

50
Q

How are water-soluble molecules transported across cell membranes?

A

They must be actively transported.

51
Q

What are the advantages/disadvantages of IV administration?

A

Advantages: all drug gets into blood, immediate effect

Disadvantages: may not be safe, requires special training (may not be convenient)

52
Q

Which is administration leads to faster absorption, IM or SQ?

A

IM > SQ

53
Q

What drugs cannot be given IM or SQ?

A

Irritating drugs

54
Q

Why can SQ and IM injections potentially result in a lower Cmax that the same dose of drug administered by IV injection?

A

This occurs because the slower absorption means that some of the drug may have already distributed to tissues or been metabolized/eliminated by the time the full dose has been absorbed. Remember that all the ADME processes are happening simultaneously, so while absorption is occurring so too are distribution, metabolism, and elimination. Since IV injections put all the drug into the blood at once, Cmax occurs very quickly and the other processes play less of a role in its determination.

55
Q

What are the advantages of oral administration?

A
  • Common, generally safe route of administration
  • Absorption can occur throughout the GI tract - SI has a large surface area and is frequently a major site of absorption
  • Easier for owners than injections
56
Q

What is the therapeutic index?

A

The plasma drug concentration between the minimum effective concentration and the toxic concentration (maximum effective concentration)

57
Q

What are some disadvantages of oral administration?

A
  • Variable absorption between individuals, species, affected by fed/fasted status
  • Affected by GI transit times (eg., animals with diseases that affect GI motility may not adequately absorb oral drugs)
  • Some medications are broken down by stomach acids
58
Q

What is bioavailability?

A

The percentage of a drug that reaches systemic circulation.

By definition, a drug administered intravenously has a bioavailability of 100%.

59
Q

If there is a large difference between the oral and intravenous route, the drug likely has…

A

poor bioavailability.

60
Q

What is the first pass effect?

A

The first pass effect is the loss of drug that occurs via metabolism/degradation in the intestinal wall and liver during absorption from the GI tract before it reaches systemic circulation.

61
Q

What is the relationship between first pass effect and bioavailabilty?

A

Opposite

High first pass = low bioavailability

62
Q

What is one way to bypass the first pass effect?

Besides giving meds IV

A

Rectal administration, since 50% of the circulation around the rectum bypasses the liver.

63
Q

How does ionization state impact how easily a drug can cross membranes?

A

Unionized drugs are more lipid soluble, so can cross membranes more easily.

64
Q

What is an important determinant of whether drugs
accumulate in certain spaces (eg., abscesses, prostate, milk)?

A

Ionization state

65
Q

What is the definition of pKa?

A

pKa is the pH at which 50% of a compound (acid or base) is ionized

66
Q

The relationship between pH and pKa determines…

A

whether the drug is predominantly ionized or non-ionized in that environment.

67
Q

Acidic drugs will be in which ionization state when they are in acidic environments?

A

Un-ionized

Like is un-ionized in like.

68
Q

Basic drugs will be in which ionization state when they are in acidic environments?

A

Ionized

Like is un-ionized in like.

69
Q

Which form predominates if pH is greater than pKa?

A

Deprotonated

70
Q

Which form predominates if pKa is greater than pH?

A

Protonated

71
Q

How does pKa influence drug distribution?

A

Acidic drugs will be in their ionized form in the blood (pH>pKa) and will have reduced distribution (can’t cross membranes as easily).

72
Q

What influences the speed of distribution?

A
  • Blood flow/organ perfusion
  • Ability of the drug to bind to the specific tissue, and to plasma proteins
  • Extent of distribution (eg., if gets into fat, which has low blood flow, will be slow to equilibrate)
  • Rate of diffusion across membranes
  • Active transport of the drug across membranes
73
Q

What is Vd?

A

The theoretical volume that would be needed to contain the total amount of administered drug at the initial concentration (C0) in the plasma after IV administration (or at Cmax after other forms of administration)

Represents the degree of TISSUE distribution of the drug
— Higher Vd means more distribution of the drug from the blood into the tissues

74
Q

What is the formula for Vd?

A
75
Q

Higher Vd means (more or less) of the drug is distributed in the tissues?

A

more

76
Q

Does Vd indicate drug penetration into certain sites?

A

Does not indicate which specific sites, just that it is leaving the bloodstream.

77
Q

What is ion trapping?

A

The side of a membrane favoring ionized drug will tend to accumulate more drug than the side favoring non-ionized drug

78
Q

What are some consequences of ion trapping?

A
  • a basic drug will accumulate in an acidic environment (e.g. a basic drug will stay in an abscess)
  • an acidic drug will be absorbed from an acidic environment (eg aspirin absorbed from the stomach)
79
Q

EXAMPLE:

A dairy cow has a pH of milk of 6.8 and the pH of plasma is 7.4. The cow is being treated with benzylpenicillin for footrot (pKa of benzylpenicillin is 2.7)

Will the benzylpenicillin tend to distribute into the milk?
Will concentrations of the drug be higher in the milk or the plasma?

A

Benzylpenicillin is an acid. Since its pKa is lower than the pH in both milk and plasma, the ionized form of benzylpenicillin will predominate in both spaces. However, because the pKa of benzylpenicillin is further from the pKa of plasma than of milk, the benzylpenicillin will be more ionized in the plasma than in milk. The non-ionized portion of benzylpenicillin will distribute between the two compartments to reach equilibrium, but when there will be a greater concentration of ionized benzylpenicillin in the plasma; therefore, the total drug will be higher in the plasma than in milk.

80
Q

How does protein binding impact distribution?

A

When a drug is highly protein bound (>90%) it is essentially sequestered in the blood and can’t distribute to tissues.

Only free, non-bound drug can distribute to tissues and interact with targets to have a pharmacodynamic effect.

81
Q

What are the two phases of metabolism?

A

Phase 1 - oxidation and reduction
Phase 2 - conjugation

These do not always occur in order!!!

82
Q

What is metabolism

A

Metabolism is the biotransformation of drugs to facilitate elimination

83
Q

How does metabolism facilitate elimination (what is the outcome of the reactions)?

A

Metabolism works to facilitate elimination, generally by reactions that increase the polarity/water solubility of the drug

84
Q

What factors impact metabolism?

A
  • Age
  • Health
  • Species
85
Q

How does age impact metabolism?

A

Metabolic enzymes may not be fully functional in neonates

86
Q

How do different species impact metabolism?

A

There are species-differences in ability to metabolize drugs.

Can’t extrapolate safe or effective doses between species!!!

86
Q

How does health impact metabolism?

A

Certain conditions, especially liver disease can reduce
ability to metabolize drugs

87
Q

What is a major enzyme involved in phase 1 metabolism?

A

Cytochrome P450

88
Q

What is important to consider about cytochrome P450?

A

The specific enzymes vary between species
Properties of CYP families are also not identical between species
Can be up- or down-regulated by drugs, dietary exposures, disease, etc.

89
Q

What is the result of up or down regulation of cytochrome P450?

A

Up-regulation increases elimination = loss of therapeutic effect

Down-regulation decreases elimination = toxicity

90
Q

What are the effects of phase 2 metabolism?

A
  • Increases water solubility by conjugating the drug to exogenous endogenous substrates
  • Also deactivates active metabolites
91
Q

What are the three most important types of conjugation reactions?

A
  1. Glucuronidation
  2. Sulfate conjunction
  3. Acetylation
92
Q

Cats are poor at which type of conjugation reaction?

A

Glucuronidation

93
Q

What is an important transport protein?

A

p-glycoprotein, an efflux transporter

94
Q

What is the role of p-glycoprotein?

A

It moves substrates (metabolized or non-metabolized drug) OUT of the cell since it is an efflux transporter

  • At the SI this limits absorption
  • At the liver this facilitates excretion into bile
  • At the kidney this facilitates excretion into urine
  • At the BBB expression by the brain capillary endothelial cells limits access to the brain
95
Q

Where are large drug molecules typically excreted?

A

Bile

96
Q

Where are small drug molecules typically excreted?

A

Urine

97
Q

Which drugs are not filtered at the glomerulus?

A

All drugs are filtered at the glomerulus, except when they are protein bound

98
Q

What is enterohepatic recirculation?

A

When drug that is excreted into the small intestine with bile is reabsorbed by the small intestine which prolongs exposure to drug

99
Q

What can create a double peak on concentration-time profiles?

A

Enterohepatic recirculation

100
Q

What percentage of THC undergoes enterohepatic recirculation in dogs?

A

10-15%

443 - Pharmacology & Toxicology (12 decks)

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