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[Ther 201] 1st Exam Transes > Pharmacokinetics I (Herbert Ho, MD) > Flashcards

Pharmacokinetics I (Herbert Ho, MD) Flashcards

1
Q

What are the two steps other than ADME that some sources include in pharmacokinetics?

A
  1. Liberation

2. Response

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2
Q

Why aren’t liberation and response included in pharmacokinetics?

A

Liberation is part of biopharmaceutics, while response is part of pharmacodynamics.

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3
Q

Enumerate the enteral routes of drug administration

A
  1. Oral
  2. Nasogastric tube
  3. Gastrostomy tube
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4
Q

Enumerate the parenteral routes of drug administration

A
  1. Intravenous (IV)
  2. Intramuscular (IM)
  3. Subcutaneous (SC)
  4. Intradermal (ID)
  5. Intra-arterial (IA)
  6. Topical (controversial)
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5
Q

If drug A is transformed into metabolite B, what is the mode of elimination?

A

Metabolism

Not excretion because the drug was changed

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6
Q

T/F: If Drug X is metabolised into an inactive metabolite and this inactive metabolite is excreted by the kidneys, the mode of elimination is both metabolism and excretion.

A

True

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7
Q

In enterohepatic recirculation, where is the compound (1) conjugated, (2) excreted, (3) deconjugated, and (4) reabsorbed?

A

(1) liver
(2) bile
(3) intestines
(4) into the circulation

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8
Q

T/F: Enterohepatic circulation decreases the half-life of a drug.

A

False

It actually increases it.

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9
Q

Bile acids are conjugated to what in the liver?

A

Taurine and glycine

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10
Q

T/F: 100% of bile salts are reabsorbed and used in cholesterol synthesis.

A

False

Only 95% are reabsorbed.

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11
Q

What may cause lower oestrogen circulating concentration leading to breakthrough pregnancy when taking oral contraceptive pills?

A

Antibiotic use, which leads to elimination of natural bacterial flora in the GIT

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12
Q

Enumerate the properties that make certain substances better absorbed

A
  1. Non-ionized
  2. Small
  3. Lipid-soluble
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13
Q

Enumerate the properties that make certain substances poorly absorbed

A
  1. Ionized

2. Large

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14
Q

Why are penicillin G and insulin poorly absorbed?

A

They are destroyed by stomach acid and/or digestive enzymes.

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15
Q

Why are tetracyclines poorly absorbed?

A

They are chelated to food components to form insoluble complexes.

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16
Q

Give examples of polar drugs that won’t cross cell membrane.

A

Aminoglycoside antibiotics such as streptomycin and gentamycin

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17
Q

What compounds undergo extensive metabolism, which is the reason for their poor absorption?

A
  1. Nitroglycerin
  2. Adrenaline
  3. Dopamine
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18
Q

Is distribution reversible or irreversible?

A

Reversible

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19
Q

Enumerate the factors affecting drug distribution

A
  1. Ionization
  2. Capillary permeability
  3. Blood flow
  4. Plasma protein binding
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20
Q

What is the only scenario where displacement of a drug from plasma protein binding will cause adverse effects?

A

When it has a very small volume of distribution or nowhere to go

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21
Q

Would the impact be greater if there’s a change in plasma protein binding (decrease of 1% bound protein) for a drug that’s 90% protein bound or 99% protein bound?

A

99% protein bound

This is because a 1% change equates to 2% free drug, which is a 100% increase in the amount of free drug.

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22
Q

What is the main organ of metabolism?

A

Liver

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23
Q

Where are the capillaries very leaky?

A

Liver and spleen

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24
Q

T/F: Drugs leave the capillaries regardless of whether they are poorly lipid soluble, charged or polar.

A

True

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25
Q

How do glucose and amino acids pass the blood brain barrier?

A

They have specific carrier-mediated transport systems.

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26
Q

What substances are tightly controlled in the brain?

A

Potassium, hydrogen and bicarbonate ions

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27
Q

In order to use dopamine and serotonin for treatment of nervous system disorders, what should you administer?

A

Precursors (L-DOPA and 5-hydroxytryptophan)

These are prodrugs.

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28
Q

What are the advantages of administering a prodrug?

A
  1. More stable
  2. More favorable PK
  3. Simpler dosage regimen
  4. May increase bioavailability
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29
Q

Describe: Acyclovir

A
  1. Used to treat chicken pox

2. Prodrug is only administered 2 times compared to 5 times for the active drug

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30
Q

How can radioactive iodine-labeled albumin help detect brain tumours?

A

Newly formed capillaries to tumours are leaky

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31
Q

Describe the hierarchy of organs in terms of the rate at which they receive the administered drug

A

Brain, liver, kidneys, and lungs > skeletal muscle > fat

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32
Q

Where is the drug concentration normally measured?

A

Blood

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33
Q

What is the formula for volume of distribution?

A

Vd = Dose/Cp

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34
Q

T/F: Correspondence of Vd with the volume of a certain body compartment may be purely coincidental

A

True

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35
Q

T/F: Gentamycin does not enter cells.

A

True

It is lipid-insoluble.

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36
Q

T/F: Ethanol Vd correspondence to total body water represents distribution in that compartment.

A

True

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37
Q

T/F: Warfarin is present in large amounts in the different tissues.

A

False

It is extensively bound to plasma proteins.

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38
Q

Give examples of drugs with physiologically impossible values.

A

Quinacrine - 300 L/kg

Amiodarone - 100 L/kg

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39
Q

What are the implications of low and high Vd with respect to intravascular concentration?

A

Low Vd - highly protein bound

High Vd - highly tissue bound

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40
Q

The smallest volume in which a drug may distribute is the (1).

A

Blood plasma volume

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41
Q

Define: Biotransformation

A

It is the chemical modification of drugs by enzymes to make them more polar.

42
Q

Where can drug metabolising enzymes be found?

A
  1. Liver
  2. GIT wall
  3. Lungs
  4. Kidneys
  5. Skin
  6. Blood
  7. Brain
43
Q

What are the two phases of metabolism or biotransformation?

A
  1. Functionalization

2. Conjugation

44
Q

What are the processes involved in functionalization?

A
  1. Oxidation
  2. Reduction
  3. Hydrolytic reactions
45
Q

What are the processes involved in conjugation?

A
  1. Glucoronidation
  2. Sulfation
  3. Acetylation
  4. Methylation
  5. Amino acid conjugation (glycine, taurine and glutathione)
46
Q

T/F: Functionalization leads to inactivation, while conjugation does not.

A

False

It’s the other way around. Both, however, make the drug more polar.

47
Q

T/F: Conjugation may precede functionalization.

A

True

48
Q

T/F: Kidney can only eliminate polar substances.

A

True

49
Q

What enzymes are largely responsible for phase 1 or functionalization reactions?

A

Liver Microsomal Cytochrome P450 Monooxygenases (CYPs)

50
Q

What is the mechanism of action of CYPs?

A

They transfer electrons from NADPH to O2 and oxidise drugs (hydroxylation and dealkylation)

51
Q

Where in the cell are phase 1 enzymes located?

A

Endoplasmic reticulum

52
Q

Which enzyme makes drug interactions most probable?

A

CYP3A4

53
Q

Describe the hierarchy of CYPs in terms of percentage of drugs metabolised

A
  1. CYP3A4
  2. CYP2D6
  3. CYP2C9 and CYP2C19
  4. CYP2E1, CYP2A6 and CYP1A2
54
Q

Enumerate non-CYP biotransformation processes

A
  1. Hydrolysis
  2. Reduction
  3. Oxidation (flavinemonooxygenase, monoamine oxidase and alcohol & aldehyde dehydrogenase)
55
Q

What processes lead to drug interactions?

A

Enyzme inhibition and activation.

56
Q

What is the effect of inducers on elimination rate?

A

Increase

57
Q

Why are inducers slower acting than inhibitors?

A

Transcription/translation and increased synthesis of heme must first take place.

58
Q

Give examples of inducers

A

Rifampicin, barbiturates and St. Johns wort (herbal antidepressant)

59
Q

Give examples of inhibitors

A
  1. Grapefruit juice
  2. Cimetidine
  3. Erythromycin
  4. Itraconazole
60
Q

Give an example of a phase 2 enzyme

A

N-acetyltransferase 2 (NAT2)

61
Q

Describe: N-acetyltransferase 2

A
  1. Slow metabolism of drugs such as isoniazid, procainamide and caffeine
  2. Slow acetylators have higher risk of bladder cancer
  3. Fast acetylators have higher risk of colorectal cancer
62
Q

When taking a drug metabolised by C P450, what should be considered?

A

Interactions due to food items or herbal medicines

63
Q

What is phase 3 metabolism?

A

Transport of drug from one compartment to another

64
Q

Give examples of secondary or tertiary active transporters

A
  1. Organic cation transporter (OCT)
  2. Organic anion transporting polypeptide family (OATP)
  3. Organic anion transporter (OAT)
  4. Peptide transporter
  5. Sodium phosphate co-transporter
65
Q

Give examples of primary active transporters

A
  1. P-glycoprotein
  2. Multidrug resistance associated protein 1 (MRP1)
  3. Canalicular multi specific organic anion transporter (cMOAT/MRP2/cMRP/MRP3)

NOTE: They are implicated in resistance of cancers due to pumping out of anticancer drugs.

66
Q

Describe: P-glycoprotein

A
  1. ATP-requiring efflux pump
  2. Broad drug specificity (digoxin, quinidine, etc.)
  3. Located in cancer tissue among other sites
  4. Induced by: rifampicin and St. Johns wort
  5. Inhibited by: verapamil, quinidine, macrolides and antifungals
67
Q

T/F: In a one compartment model, drug distribution is assumed to be instantaneous.

A

True

68
Q

T/F: Most drugs support the two compartment model.

A

False

Most drugs support the one compartment model.

69
Q

T/F: In pharmacology, linearity is in the semilog sense.

A

True

70
Q

What is the equation for a one compartment model?

A

C = Coe^-kt

71
Q

What is the equation for a two compartment model?

A

C = Ae^-bt + Be^-at

72
Q

What is a first-order reaction?

A

Rates are linearly related to dose administered

73
Q

What is the rate of change for first-order equations?

A

dA/dt = -kA

74
Q

What is the value of e?

A

e = 2.718

75
Q

What is the semi-log equation for a one compartment model?

A

ln(C) = ln(Co) - kt

76
Q

Define: half-life

A

Amount of time required for a drug to be reduced to half its original concentration

77
Q

Give the formula for half-life of 1st order reactions

A

t1/2 = 0.693/k

78
Q

What are the important assumptions for a one compartment model with first-order input and first-order elimination?

A
  1. Dose is gradually absorbed
  2. Driving force is concentration gradient
  3. There is a single homogenous compartment
79
Q

What is the formula for a one compartment model with first-order input and elimination?

A

Cp = [(F x dose x ka)/Vd(ka-k10)][e^-k10t - e^-kat]

80
Q

What is another way of expressing the rate of elimination?

A

CL x Cp

81
Q

What does it mean if a drug has low tmax?

A

It is absorbed quickly.

82
Q

What is the relationship between distribution and elimination?

A

Distribution precedes elimination, but both happen all throughout.

83
Q

Describe a “physiologically-based pharmacokinetic model”

A

It is derived from anatomy and physiology of the organism and not from drug data.

84
Q

In a multi-compartment model, what is the total distribution space for drugs?

A
  1. Central compartment (organs with high blood flow)

2. Peripheral compartment (absorption > elimination; i.e. adipose tissues and muscles)

85
Q

T/F: Drug distribution is instantaneous in a multi-compartment model.

A

False

Volume bound to proteins > volume in steady state > volume in central compartment

86
Q

What do you call the clearance leaving the central component in a multi-compartmental model?

A

Central or metabolic clearance

87
Q

In the log concentration vs. time plot, the number of kinks varies with the number of (1)

A

(1) compartments

88
Q

What is the only assumption in the non-compartmental model?

A

First-order single exponential terminal phase is present. Terminal phase should resemble a 1C model.

89
Q

When is the non-compartmental model useful?

A

When little is known about the drug.

90
Q

T/F: Prior to the last 10 years, the method of choice was the 1C model.

A

False.

It was the non-compartmental model.

91
Q

Define: Area Under the Curve (AUC)

A

It is a measure of exposure of our body to the drug.

92
Q

What concept is used to compute for the area under the curve?

A

Trapezoidal concept

93
Q

What is the formula for AUC from 0 to t?

A

Sigma (0-t) [0.5(Ct1 + Ct2)] x delta time

94
Q

What is the formula for AUC from t to infinity?

A

AUC (t-infinity) = Clast/ke

95
Q

Why is the logarithmic trapezoidal method more accurate when concentrations are decreasing?

A

Drug elimination is exponential.

96
Q

What is the formula for AUC based on the logarithmic trapezoidal method?

A

AUC (t1 - t2) = [(Ct1 - Ct2)] x delta time/ln (Ct1/Ct2)

97
Q

T/F: For submissions to the FDA, using the linear trapezoid method will suffice.

A

True

98
Q

When is drug concentration assumed to be negligible?

A

After 4 - 7 half-lives

99
Q

What is the formula for clearance?

A

Cl = Vd x ke

Cl = 0.693Vd/t1/2

Cl = rate of elimination/C

100
Q

T/F: Clearance is the same as elimination.

A

False

Clearance is usually constant, while elimination rate is variable.

101
Q

Describe the relationship of ka, Cmax and Tmax.

A

A higher ka would lead to higher Cmax and shorter Tmax

102
Q

T/F: ka and Cpmax may be different for three graphs, but their AUCs may be equal.

A

True

[Ther 201] 1st Exam Transes (11 decks)

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