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PHAC3001 > Lecture 3: Pharmacokinetics Part 1 > Flashcards

Lecture 3: Pharmacokinetics Part 1 Flashcards

1
Q

Pharmacokinetics

A
  • What the body does to drugs

- The quantitative study and characterization of the time course of drug concentrations in the body

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2
Q

What is the ultimate goal of pharmacologic therapeutics?

A

To achieve a desired beneficial effect with minimal adverse effects

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3
Q

Differences in ____ play a major role in a patient’s response to drugs

A

genetics

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4
Q

The majority of variability seen in patient populations with respect to their drug response are ___________ in nature

A

pharmacokinetic

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5
Q

Define drug absorption

A

The movement of drugs from the site of administration to the site that we measure the drug concentration in the body; we typically measure drug concentrations in the blood

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6
Q

Define drug distribution

A

The reversible movement of drugs from the blood to tissues and other extravascular tissues in the body. This process is reversible. Drugs must be able to distribute to their intended target site.

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7
Q

Define drug elimination

A

The removal of the drug from the blood through drug metabolism and drug excretion. Drug elimination has the greatest variation between individuals and is the major deciding factor in the difference between pharmacokinetics in individuals

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8
Q

4 factors of pharmacokinetics

A
  • Absorption
  • Distribution
  • Metabolism
  • Excretion

Acronym: ADME

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9
Q

Routes for drug administration

A

Systemic: Enteral or parenteral
Local: topical

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10
Q

Enteral route of drug administration properties

A
  • The desired effect is systemic (non-local)

- The substance is given via the digestive tract

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11
Q

The most common and convenient route for enteral drug administration is:

A

Oral

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12
Q

The first pass effect

A
  • A major downfall of oral drug administration
  • The drugs are required to “first pass” through your small intestine and liver, which both produce enzymes capable of breaking the drug down, prior to getting into the circulation.
  • The metabolism by enzymes reduces the amount of the drug that gets into the systemic circulation; the enzymes limit bioavailability.
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13
Q

The enteral oral route is not suitable for drugs that (3):

A
  • Are rapidly metabolized
  • Drugs that are acid labile (would be broken down in the highly acidic environment of the stomach)
  • Drugs that cause irritation of the gastrointestinal tract
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14
Q

3 examples of enteral routes

A
  • Oral
  • Gastric feeding tube
  • Rectal
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15
Q

Parenteral route of drug administration properties

A
  • Desired effect is systemic (non-local)

- Drug is given via a route other than the digestive tract

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16
Q

The most common rout for parenteral drug administration is

A

Injection

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17
Q

Injection is most commonly administered (3 ways):

A

Intravenous, intramuscular, subcutaneous (just under the skin)

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18
Q

______ injection is the most rapid means for delivery of drugs to systemic circulation

A

Intravenous injection

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19
Q

Why does intravenous injection allow for 100% bioavailability?

A

Intravenous injection bypasses the first-pass effect. If you inject 100mg, then 100mg will go directly into the blood and be metabolized from there.

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20
Q

Acid labile drugs are best administered via

A

Injection, as they would be metabolized if given via the enteral route.

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21
Q

Downfalls of drug administration via injection (3)

A
  • May require professional administration
  • Costs associated with injection materials and disposal
  • Requires sterile preparation
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22
Q

Parenteral routes of drug administration (2 categories)

A

Transdermal (e.g. nicotine patches and Transmucosal

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23
Q

Three types of transmucousal drug administration

A
  • Buccal (nitroglycerine tablets; under tongue or on cheek)
  • Insufflation (cocaine; nasal membranes)
  • Inhalational (general anesthetics; inhaled to lungs)
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24
Q

Where are topical drugs administered and where is the drug action desired?

A

Topical drugs have a local effect and thus are applied directly where the action is desired

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25
Q

Ways to apply topical drugs (6)

A
  • Epicutaneous (application on skin)
  • Inhalational
  • Eye drops
  • Ear drops
  • Intranasal
  • Vaginal
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26
Q

The most common drug absorption method is

A

Oral drug absorption

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27
Q

Define oral drug absorption

A

The process of a drug moving from the site of administration (GI tract) to the site of measurement (the blood).

28
Q

In order to be absorbed into the body, drugs have to pass through _____ cells in the intestinal wall. If it isnt absorbed, it will be ______.

A
  • Enterocytes

- excreted in the feces

29
Q

Most oral drug absorption occurs by _____ across membranes

A

Passive diffusion

30
Q

Efficiency of drug absorption is effected by its

A

Physiochemical properties

31
Q

The rate and extent of oral drug absorption is affected by:

A
  • Concentration differences across membrane
  • Size of drug
  • Polarity/chemical structure
  • Ionization potential
32
Q

The primary driving force for passive diffusion across membranes which is used very largely for most drugs is

A

concentration differences across membranes. When a drug moves passively, it moves from areas of high concentration to low concentrations.

33
Q

(Polar/non-polar) drugs are less efficiently absorbed

A

Polar

34
Q

Chemical groups that impart polarity on drugs

A
  • OH (hydroxyl) , C=O (carbonyl)

- More of these = more polar = not as good at being absorbed

35
Q

T/F: Highly ionized drugs are less efficiently absorbed

A

True

36
Q

Chemical groups that increase ionization of drugs

A

Carboxylic acid groups, amine groups.

-more groups = greater ionization = less efficiently absorbed

37
Q

Ionization is highly dependent on _____

A

Environmental pH

38
Q

Carboxylic acid groups are more likely to be ionized in a ___ environment.

A

basic

39
Q

Amine groups are more likely protonated/ionized in an ____ environment

A

acidic

-An example of this is the stomach

40
Q

(T/F) Efficiency of drug absorption changes depending on where in the GI tract a drug is located due to differences in pH

A

True. The stomach is highly acidic while the duodenum is neutral and the rest of the small intestine is neutral-basic, so the ionization of drugs is going to be different in these different environments

41
Q

Why does the majority of drug absorption occur within the small intestine? What increases the surface area of the small intestine?

A

The small intestine has an extremely large surface area which favours passive diffusion. called villi, and projections attached to these called microvilli, greatly enhance the surface area of the small intestine.

42
Q

Why is rapid blood flow to the small intestine beneficial for drug absorption?

A

The rapid blood flow quickly carries away absorbed drugs, maintaining the concentration gradient so that more of the drug will be absorbed into the blood

43
Q

Factors that can lead to different oral drug absorption of the same drug

A
  • Gastrointestinal motility
  • Metabolism (first pass effect)
  • Changes in GI pH
44
Q

Why does gastrointestinal motility cause a variation in oral drug absorption between individuals?

A
  • Decreased stomach emptying slows onset/rate of drug absorption
  • GI motility can be decreased by food, disease, and drugs (such as opioids)
45
Q

Differing GI tract pH can cause differences in drug absorption because

A

pH affects ionization (charge) of acidic and basic drugs

46
Q

Drug distribution

A

Process by which a drug reversibly leaves the blood and is distributed throughout the tissues of the body. Critical requirement for achieving a therapeutic benefit.

47
Q

The extent to which drug distribution occurs is dependent on 4 factors:

A
  • Blood flow
  • Ability of drug to traverse cell membranes (same factors as passive absorption)
  • Degree of binding to blood proteins (e.g. serum albumin)
  • Unique properties of drug/tissue
48
Q

Volume of Distribution (Vd)

A

-The apparent volume of fluid into which an administered drug is dispersed. “Apparent” because it assumes equal partitioning throughout the body (i.e. plasma concentration is equal to that of all other volumes)

49
Q

How is Vd determined?

A

From measurement of initial plasma drug level immediately after IV bolus injection.

Vd=Q/Co
where Q= total amount of drug in body and Co= initial plasma concentration

50
Q

When talking about Vd, we are talking about 3 different volumes:

A

Intracellular, plasma, and interstitial

51
Q

If we assume equal partitioning of a drug throughout the body, then in a 70 kg male with 42 L of body we would assume Vd for every drug was

A

42 L

52
Q

A small Vd (< 42 L) infers:

A

Retention within the plasma volume (not distributing effectively)

53
Q

A large Vd (>42 L) infers

A

Retention in volumes outside of plasma (extensive distribution, may be accumulating in a tissue)

54
Q

In order to do accurate dosage concentrations, it is important to know:

A

The volume of distribution for the drug.

Co= Q/Vd. If we know Vd and Q (dose) we can determine what the initial plasma concentration will be.

55
Q

As Vd increases, the ____ of drug required to achieve a particular ______ also increases

A
  • Dose (Q)

- Initial plasma concentration (Co)

56
Q

Factors that contribute to a high volume of distribution

A
  • Physiochemical properties of a drug

- Physiological properties of tissues

57
Q

What physiochemical properties favour a high Vd?

A
  • High lipophilicity
  • Low polarity
  • Low ionization
  • Low molecular weight

These properties allow for an increased ability to traverse biological membranes of cells (blood vessels, tissues)

58
Q

Drugs will accumulate in tissues where there is a lot of something they have a high affinity for. For example:

A

Tetracycline has a high affinity for binding calcium, so it will accumulate in teeth and bones

59
Q

Why are some drugs sequestered by the thyroid gland?

A

The thyroid gland makes hormones that contain iodine, so it must sequester iodine from the blood. If a drug contains iodine, it could be sequestered by the gland, and the drug would accumulate in the thyroid.
E.g. amiodarone (Vd=5000 L) can cause thyroid toxicity

60
Q

What kinds of drugs accumulate in adipose tissue?

A

Drugs that are lipid soluble can accumulate in adipose tissue. E.g. chloroquine (Vd=15,000) accumulates in the adipose and comes out very slowly.

61
Q

Why does Vd for chloroquine vary significantly between people?

A

If someone is fat (has more adipose tissue) their Vd for chloroquine will be much higher compared to someone with less adipose tissue. Leads to differences in dosage requirements.

62
Q

Factors that contribute to a low volume of distribution

A
  • Physiochemical properties of a drug

- Binding to blood proteins

63
Q

What physiochemical properties contribute to low Vd? (4)

A
  • Low lipophilicity
  • High polarity
  • High ionization
  • High molecular weight

These properties do not favour passive diffusion and cause drugs to stay in the blood

64
Q

Describe how albumin contributes to a low Vd

A
  • Drugs bind blood serum albumin
  • Albumin-bound drugs are generally therapeutically inactive
  • Binding to albumin is reversible. Other drugs can displace the albumin-bound drug and the previously bound drug becomes activated
65
Q

Why is displacement of a drug bound to albumin potentially dangerous?

A

When another drug comes and binds to albumin instead, the initial drug becomes free and active in the blood which can lead to a potentially dangerous increase in blood concentration of the active drug.

66
Q

We are especially concerned about about albumin-bound drugs being displaced when:

A

The drug is highly bound (>90%) and has a small/narrow therapeutic window/index
E.g. warfarin has a small VD (=8 L) because it is bound to serum albumin.

PHAC3001 (5 decks)

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