Brainscape's Knowledge GenomeTM

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


See full index

Pharm Block 1 > Pharmacokinetics > Flashcards

Pharmacokinetics Flashcards

1
Q

Cell Membrane Polarity

A 
Charged heads (hydrophilic)
Uncharged tails (lipophilic)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Types of compounds that diffuse passively through membrane

A

Lipophilic (uncharged)

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

Determinants of passive diffusion

A

Partition coefficent

Concentration gradient

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

Form of weak acid that diffuses

A

HA

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

Form of weak base that diffuses

A

B

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

Definition of pKa

A

pH where ratio of unprotonated to protonated is equal

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

Henderson-Hasselbach equation

A

log([protonated]/[unprotonated]) = pKa - pH

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

Ion trapping of drugs

A

Acidic drugs accumulate on the side of the membrane that is more basic
Basic drugs accumulate on the side of the membrane that is more acidic

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

Characteristics of passive diffusion

A

Bidirectional

Driven by concentration gradient

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

Definition of carrier mediated transport

A

Molecule across a barrier is mediated by the binding of solute to protein transporter

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

Purposes of carrier mediated transport

A

Hydrophilic molecule movements
Molecules against gradient
Providing specificity

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

Characteristics of facilitated diffusion

A

Carrier mediated
Concentration gradient driven
Not active energy
Example: Glucose transport

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

Characteristics of active transport

A

Carrier mediated
Moves solute against its concentration gradient
Active energy

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

What is p-glycoprotein?

A

ATP binding cassette (ABC) carrier or pump
Binds to lipophilic drugs to promote their efflux (removal) from cell
Energy from ATP hydrolysis
Encoded by multidrug resistance gene

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

Characteristics of secondary active transport

A

Carrier mediated
Multiple solutes in same (symport) or opposite (antiport) directions
Requires moving one solute down its gradient to drive the movement of the other against its concentration gradient

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

Most often driving solute for secondary active transport

A

Sodium or hydrogen

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

Name of symport and antiport proteins

A

Symport: Co-transporter
Antiport: Exchangers

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

Definition of bioavailability

A

F - Fraction of the administered dose of drug that reaches circulation

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

What is an F = 1 defined to be?

A

IV delivery

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

Bioavailability of oral drugs

A

F < 1

Incomplete absorption, first pass effect

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

Definition of first pass effect

A

Orally administered drugs are metabolized by liver or excreted into intestine via biliary excretion (enterohepatic circulation)
Results in not reaching systemic circulation

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

Propranolol’s bioavailability

A

Loss during first pass

Causes it to have low potency

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

Therapeutic considerations of first pass effect

A

More for older, established drugs

Newer drugs are designed with this in mind so structure minimizes the effect

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

Definition of bioequivalence

A

Same drug
Same route of administration
Same amount of drug enters the circulation
Drug enters the circulation at same rate
Standard for comparing formulations (generics)

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

Absorption of orally administered drugs

A 
Passive diffusion in GI tract
Unionized form (No not the auto workers)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Characteristics of Stomach Absorption

A

Very acidic, thick mucous, small surface area

Limited absorption of even weak acids

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

Characteristics of Upper Intestine Absorption

A

pH of about 7
Large absorptive surface area (200 sq meters)
Moving blood prevents formation of an equilibrium (Le Chatelier all day to the blood)

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

Gastric emptying impact on drug absorption

A

Increased emptying increases the rate of absorption

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

Effect of dissolution of a solid drug

A

Affect the rate of absorption

Coatings, particle sizes need to be considered

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

How to achieve controlled release solid drug?

A

Hard-to-dissolve agents for slow uniform dissolution and absorption

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

Advantages of controlled release solid drug

A

Slower absorption results in decreased frequency of dosing, more uniform concentration of drug in the blood

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

Disadvantages of controlled release solid drug

A

Greater variability among patients (Grapefruit and dat Cytochrome P450 action)
Greater toxicity if incorrectly absorbed (Chewing the pill)

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

Purpose of enteric coatings

A

Protect the drug from the stomach acid and stomach from drug (e.g. aspirin)
Better taste

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Sublingual delivery definition

A

Under the tongue (e.g. nitroglycerin for angina)

Rapid absorption

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

Buccal delivery definition

A

Beneath gum and cheek

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

Characteristics of sublingual/buccal delivery

A

Blood drains into the sup. vena cava
Avoids liver for first pass
Small surface area so drug is lipophilic

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

Rectal administration advantages

A

Useful if patient cannot or won’t swallow (unconscious, vomiting, pediatric, etc.)
50% less first pass than orally administered agents

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

Rectal administration disadvantages

A

Variable absorption, can be incomplete, irritating to rectal mucosa, uncomfortable

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

Transdermal administration definition

A

Through the skin

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

Characteristics of transdermal

A

Epidermis is impermeable to hydrophilic, but permeable to lipophilic
Best if hydrated
Examples are nicotine, estrogen/progesterone

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

Definition of parenteral injection

A

Without the intestine

Include IV, subcut, and intramuscular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Mechanism of subcutaneous and intramuscular delivery

A

Injection results in a depot of drug in dermis or muscle

Drug diffuses to nearby capillaries

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Rate of absorption of lipophilic drugs via injection

A

Depends on drug solubility in interstitial fluid

Area of capillary bed in vicinity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Mechanism of absorption of large hydrophilic drugs via injection

A

Pass through large, aqueous channels in the capilaries

Example insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Mechanism of absorption of proteins via injection

A

Enter via the lymphatic system

Example: Antigens in vaccination

46
Q

Where do the parenterally drugs distribute to first?

A

The Lungs

47
Q

Characteristics of lung during drug absorption

A

Metabolically active organ, large capillary bed
Filters particulates
Volatile agents can diffuse into the expired air (breathilizer test)
Lipophilic agents can accumulate; redistribute

48
Q

Characteristics of IV injection

A

Completely bioavailable (F = 1)
Achieve immediate action; drug delivery can be highly controlled
Dose and rate of delivery can be rapidly adjusted
Anesthetics; emergency treatments
Irritating agents are diluted by the entire blood volume

49
Q

Advantages of IV injections

A

Control over dosage

Control over rate of administration (Bolus. slow infusion)

50
Q

Disadvantages

A

Route of no return, hard to remove once in circulation

Need close monitoring, experienced staff

51
Q

Subcutaneous control of absorption

A

Add vasoconstrictors to delay absorption

52
Q

Variability of intramuscular absorption

A

Blood flow based on muscle demand

53
Q

Airway administration purposes

A

Volatile agents; rapid access to the circulation

Treatment of the airway (targeted delivery in brachoconstriction)

54
Q

Topical targets for drugs

A

Mucous membranes

Eye

55
Q

Definition of drug eluting stents

A

Placing a scaffold into the artery (stent) with drugs bound onto the stent for controlled release
Example: Anticoagulants post balloon angioplasty

56
Q

Drug delivery targeting of cells via ________

A

Antibodies

Possible treatment for tumor cells

57
Q

Prodrug delivery

A

Inactive drugs that are activated by enzymes at target site

Example; Heroin in the brain

58
Q

Blood flow phases of drug delivery

A

First phase: Highly perfused organs receive most of the drug; equilibration is rapid
Second phase: More poorly perfused organs; equilibration is very slow

59
Q

Role of capillary permeability of drug delivery

A

Endothelial junctions are loose so paracellular delivery (except in brain) - Driven by hydrostatic pressures
Lipids can transfer transceullularly

60
Q

Role of plasma proteins in drug delivery

A

Drug binding to plasma proteins (low affinity, easily reversible)
Follows mass action

61
Q

Specific proteins for acidic and basic drugs

A

Albumin - Acidic (Has positive charge sites)

Alpha-1-Acid-Glycoprotein - Basic (Has negative charge sites)

62
Q

Equation for drug binding

A

[DP] = [Total protein]*[Drug]/(Kd+[Drug])

[DP] remains constant if drug is repeatedly delivered ([Drug] = constant)

63
Q

Method of disease altering protein binding

A

Alters concentration of plasma binding proteins long term

64
Q

Liver disease effect on protein binding

A

Reduced albumin and reduced binding

Need to decrease the dose of drug

65
Q

Immune activation effect on protein binding

A

Increase α-1-acid glycoprotein

Need to increase drug dosage

66
Q

Examples of tissue reservoirs for drugs

A

Fat - Lipophilic drugs for long periods

Bone - Divalent cations (tetracycline) and heavy metals

67
Q

Definition of redistribution

A

Mechanism of termination of action of a drug

Redistribution from active site (tissue) to inactive site

68
Q

Examples of redistribution

A

Highly lipid soluble drugs
Drugs acting on a highly perfused organ (brain or heart)
Drugs administered by IV or inhalation (general anesthetics)

69
Q

Issues of drug distribution into CNS

A

Has to overcome tight capillary endothelial cell junctions (blood-brain barrier) and tight epithelial cell junctions (blood-CSF barrier)

70
Q

Drugs able to enter the brain

A

Unionized, not protein, bound, and highly lipophilic

Substrates for carriers (e.g. Levo-dopa)

71
Q

Brain efflux mechanisms

A

P-glycoprotein (lipophilic drugs; inducible)

Organic anion transporting polypeptide (OATP; negatively charged molecules)

72
Q

Why does loperamide (an opioid) not have any CNS effects?

A

OATP

73
Q

Factors for placental transfer of drug

A

Lipophilicity, unionized drug, protein binding for passive
Fetal plasma is more acidic than maternal; trapping of basic drugs
Carriers are present

74
Q

Renal excretion processes

A

Glomerular filtration - Unbound drug enters the tubular lumen
Active tubular secretion (Proximal tubule)
Passive tubular reabsorption (proximal and distal tubules)

75
Q

Methods of active tubular secretion

A

Moved into tubular lumen via pumps
P-glycoprotein; multi-drug resistance protein type 2 (MDRP-2, an ABC transporter)
Results in excretion rate that is greater than GFR

76
Q

Clinical importance of passive tubular reabsorption

A

Treating overdoses or poisonings (altering pH of urine) to hasten excretion

77
Q

Methods of biliary and fecal excretion

A

Canalicular membrane of hepatocytes ABC transporters to move drugs into bile
Carriers on enterocytes to move drugs from circulation into intestinal lumen
Role in enterohepatic recycling

78
Q

Other Routes of Excretion

A

Sweat, saliva, tears, hair, skin (useful for drug detection)
Milk (Lipophilic drugs enter easily)
Slightly acidic compared to blood; trapping of weak bases

79
Q

Definition of rate of absorption

A

Peak height/Time to peak = Cmax/tmax

80
Q

Definition of lag time

A

Time to peak = tmax

81
Q

Definition of extent of absorption

A

Area under concentration curve

82
Q

Definition of therapeutic window

A

Amount of time where drug concentration is between minimum effective concentration and minimum toxic concentration

83
Q

Definition of volume of distribution

A

Amount of volume in the body that contains the drug

84
Q

Equation of volume of distribution (Vd)

A

Amount of drug in the body = Vd * [Drug]

Vd = D/C0; D is the dosage

85
Q

Definition of C0

A

Concentration of drug at time zero

Determined by extrapolating the elimination phase

86
Q

Definition of accumulation phase/elimination phase

A

Accumulation - Drug plasma curve pre-peak

Elimination - Drug plasma curve post-peak (linear in log-range)

87
Q

Assumption for determining Vd

A

Concentration of drug throughout body is the same as its concentration in plasma/serum (likely incorrect)

88
Q

Notable Vd values

A

Small - Entirely in plasma (2.8 L/70kg person)
Total body volume - Moves like water (about 70 L)
Very large - Drug is being sequestered in non-plasma

89
Q

How is Vd given in dosing tables?

A

Usually as a rate dependent on patient body weight (Liters/kg)

90
Q

Drug dosage equation with bioavailability factored in

A

D = Vd * C0/F

91
Q

What does bioavailability change in a drug response curve?

A

Cmax and area under curve are directly proportional to F

Rate of accumulations and elimination are unfaffected

92
Q

Definition of clearance of drug

A

CL = rate of elimination/concentration (Volume/time)
CLs are additive if multiple routes
CL_total = CL_renal + CL_liver

93
Q

When is clearance constant?

A

If clearance processes are not saturated.

Common at therapeutic concentraions

94
Q

What order process are drugs cleared through?

A

First order-decay

Log-linear

95
Q

Slope of drug clearance in a log10 curve

A

-k_el/2.3

96
Q

Half-life of drug

A

T1/2 = 0.69/k_el
Time needed to reduce the amount of drug by one half
Constant for a first order process

97
Q

Definitions of IV phases

A

Alpha Phase - Distribution: From circulation to tissues instead of accumulation phase for oral
Beta Phase - Elimination: Same concepts as oral drug elimination phase

98
Q

Zero-order kinetics

A

Saturated elimination processes (via Michaelis-Menten kinetics)
Clearance is not a constant

99
Q

Effect on CL, k_el, T1/2 with increasing concentration in zero-order kinetics

A

CL decreases
k_el decreases
half-life increases

100
Q

Drugs that show zero-order kinetics

A

Ethanol, aspirin, phenytoin

101
Q

Therapeutic concern for zero-order kinetics

A

Drugs accumulate due to lack of elimination

102
Q

Relationship between CL and T1/2

A

CL = k_el * Vd
T1/2 = 0.69/k_el
Therefore: T1/2 = 0.69 * Vd/CL

103
Q

Effect of repeat dosing on first-order kinetics

A

Body reaches steady state where amount added and the amount eliminated are equal

104
Q

Equation of steady state concentration of drug

A

F*Dose/dosing interval = CL * Css

Rate in = Rate out

105
Q

What is a desirable value for Css?

A

Somewhere in the therapeutic window

106
Q

Definition of maintenance dose

A

Dose that keeps the Css

107
Q

How long does it take for a maintenance dose to reach Css?

A

4-5 half-lives

108
Q

How to reach Css more quickly?

A

Loading dose - Large dose which is used to reach Co

109
Q

4 Important Equations

A

Henderson-Hasselbach
Loading dose
Half-life/clearance relationship
Maintenance dose

110
Q

Effect of decreased renal function on drug response

A

Elimination rate and clearance decrease
Half-life increases
New higher steady state if same dosage maintained

111
Q

Effect of decreased dose interval (assuming accompanied decrease in dosage)

A

Narrows concentration window while keeps the same Css (same concept for controlled release)
Useful if therapeutic window is narrow

Pharm Block 1 (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions